diff --git a/Lib/uuid.py b/Lib/uuid.py
index 2c16c3f0f5a5b5..15def2d7db6432 100644
--- a/Lib/uuid.py
+++ b/Lib/uuid.py
@@ -633,22 +633,24 @@ def _netstat_getnode():
 try:
     import _uuid
     _generate_time_safe = getattr(_uuid, "generate_time_safe", None)
+    _has_stable_extractable_node = _uuid.has_stable_extractable_node
     _UuidCreate = getattr(_uuid, "UuidCreate", None)
 except ImportError:
     _uuid = None
     _generate_time_safe = None
+    _has_stable_extractable_node = False
     _UuidCreate = None
 
 
 def _unix_getnode():
     """Get the hardware address on Unix using the _uuid extension module."""
-    if _generate_time_safe:
+    if _generate_time_safe and _has_stable_extractable_node:
         uuid_time, _ = _generate_time_safe()
         return UUID(bytes=uuid_time).node
 
 def _windll_getnode():
     """Get the hardware address on Windows using the _uuid extension module."""
-    if _UuidCreate:
+    if _UuidCreate and _has_stable_extractable_node:
         uuid_bytes = _UuidCreate()
         return UUID(bytes_le=uuid_bytes).node
 
diff --git a/Modules/_uuidmodule.c b/Modules/_uuidmodule.c
index c5e78b1510b5e3..c31a7e8fea5608 100644
--- a/Modules/_uuidmodule.c
+++ b/Modules/_uuidmodule.c
@@ -78,23 +78,47 @@ py_UuidCreate(PyObject *Py_UNUSED(context),
     return NULL;
 }
 
+static int
+py_windows_has_stable_node(void)
+{
+    UUID uuid;
+    RPC_STATUS res;
+    Py_BEGIN_ALLOW_THREADS
+    res = UuidCreateSequential(&uuid);
+    Py_END_ALLOW_THREADS
+    return res == RPC_S_OK;
+}
 #endif /* MS_WINDOWS */
 
 
 static int
-uuid_exec(PyObject *module) {
+uuid_exec(PyObject *module)
+{
+#define ADD_INT(NAME, VALUE)                                        \
+    do {                                                            \
+        if (PyModule_AddIntConstant(module, (NAME), (VALUE)) < 0) { \
+           return -1;                                               \
+        }                                                           \
+    } while (0)
+
     assert(sizeof(uuid_t) == 16);
 #if defined(MS_WINDOWS)
-    int has_uuid_generate_time_safe = 0;
+    ADD_INT("has_uuid_generate_time_safe", 0);
 #elif defined(HAVE_UUID_GENERATE_TIME_SAFE)
-    int has_uuid_generate_time_safe = 1;
+    ADD_INT("has_uuid_generate_time_safe", 1);
 #else
-    int has_uuid_generate_time_safe = 0;
+    ADD_INT("has_uuid_generate_time_safe", 0);
 #endif
-    if (PyModule_AddIntConstant(module, "has_uuid_generate_time_safe",
-                                has_uuid_generate_time_safe) < 0) {
-        return -1;
-    }
+
+#if defined(MS_WINDOWS)
+    ADD_INT("has_stable_extractable_node", py_windows_has_stable_node());
+#elif defined(HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC)
+    ADD_INT("has_stable_extractable_node", 1);
+#else
+    ADD_INT("has_stable_extractable_node", 0);
+#endif
+
+#undef ADD_INT
     return 0;
 }
 
diff --git a/configure b/configure
index 8b91d1d871a971..180b5b1a432542 100755
--- a/configure
+++ b/configure
@@ -14013,6 +14013,7 @@ fi
 
 
 
+
 have_uuid=missing
 
        for ac_header in uuid.h
@@ -14022,6 +14023,7 @@ if test "x$ac_cv_header_uuid_h" = xyes
 then :
   printf "%s\n" "#define HAVE_UUID_H 1" >>confdefs.h
 
+
   for ac_func in uuid_create uuid_enc_be
 do :
   as_ac_var=`printf "%s\n" "ac_cv_func_$ac_func" | sed "$as_sed_sh"`
@@ -14031,7 +14033,9 @@ then :
   cat >>confdefs.h <<_ACEOF
 #define `printf "%s\n" "HAVE_$ac_func" | sed "$as_sed_cpp"` 1
 _ACEOF
- have_uuid=yes
+
+    have_uuid=yes
+    ac_cv_have_uuid_h=yes
     LIBUUID_CFLAGS=${LIBUUID_CFLAGS-""}
     LIBUUID_LIBS=${LIBUUID_LIBS-""}
 
@@ -14121,6 +14125,7 @@ if test "x$ac_cv_header_uuid_uuid_h" = xyes
 then :
   printf "%s\n" "#define HAVE_UUID_UUID_H 1" >>confdefs.h
 
+          ac_cv_have_uuid_uuid_h=yes
           py_check_lib_save_LIBS=$LIBS
 { printf "%s\n" "$as_me:${as_lineno-$LINENO}: checking for uuid_generate_time in -luuid" >&5
 printf %s "checking for uuid_generate_time in -luuid... " >&6; }
@@ -14218,8 +14223,9 @@ fi
 printf "%s\n" "$ac_cv_lib_uuid_uuid_generate_time_safe" >&6; }
 if test "x$ac_cv_lib_uuid_uuid_generate_time_safe" = xyes
 then :
-  have_uuid=yes
-            printf "%s\n" "#define HAVE_UUID_GENERATE_TIME_SAFE 1" >>confdefs.h
+
+            have_uuid=yes
+            ac_cv_have_uuid_generate_time_safe=yes
 
 fi
 
@@ -14263,6 +14269,7 @@ if test "x$ac_cv_header_uuid_uuid_h" = xyes
 then :
   printf "%s\n" "#define HAVE_UUID_UUID_H 1" >>confdefs.h
 
+          ac_cv_have_uuid_uuid_h=yes
           py_check_lib_save_LIBS=$LIBS
 { printf "%s\n" "$as_me:${as_lineno-$LINENO}: checking for uuid_generate_time in -luuid" >&5
 printf %s "checking for uuid_generate_time in -luuid... " >&6; }
@@ -14360,8 +14367,9 @@ fi
 printf "%s\n" "$ac_cv_lib_uuid_uuid_generate_time_safe" >&6; }
 if test "x$ac_cv_lib_uuid_uuid_generate_time_safe" = xyes
 then :
-  have_uuid=yes
-            printf "%s\n" "#define HAVE_UUID_GENERATE_TIME_SAFE 1" >>confdefs.h
+
+            have_uuid=yes
+            ac_cv_have_uuid_generate_time_safe=yes
 
 fi
 
@@ -14392,10 +14400,16 @@ else
         { printf "%s\n" "$as_me:${as_lineno-$LINENO}: result: yes" >&5
 printf "%s\n" "yes" >&6; }
                     have_uuid=yes
-      printf "%s\n" "#define HAVE_UUID_H 1" >>confdefs.h
-
-      printf "%s\n" "#define HAVE_UUID_GENERATE_TIME_SAFE 1" >>confdefs.h
-
+      ac_cv_have_uuid_generate_time_safe=yes
+      # The uuid.h file to include may be <uuid.h> *or* <uuid/uuid.h>.
+      # Since pkg-config --cflags uuid may return -I/usr/include/uuid,
+      # it's possible to write '#include <uuid.h>' in _uuidmodule.c,
+      # assuming that the compiler flags are properly updated.
+      #
+      # Ideally, we should have defined HAVE_UUID_H if and only if
+      # #include <uuid.h> can be written, *without* assuming extra
+      # include path.
+      ac_cv_have_uuid_h=yes
 
 fi
 
@@ -14416,6 +14430,7 @@ if test "x$ac_cv_func_uuid_generate_time" = xyes
 then :
 
       have_uuid=yes
+      ac_cv_have_uuid_uuid_h=yes
       LIBUUID_CFLAGS=${LIBUUID_CFLAGS-""}
       LIBUUID_LIBS=${LIBUUID_LIBS-""}
 
@@ -14426,6 +14441,24 @@ fi
 
 done
 
+fi
+
+if test "x$ac_cv_have_uuid_h" = xyes
+then :
+  printf "%s\n" "#define HAVE_UUID_H 1" >>confdefs.h
+
+fi
+if test "x$ac_cv_have_uuid_uuid_h" = xyes
+then :
+  printf "%s\n" "#define HAVE_UUID_UUID_H 1" >>confdefs.h
+
+fi
+if test "x$ac_cv_have_uuid_generate_time_safe" = xyes
+then :
+
+  printf "%s\n" "#define HAVE_UUID_GENERATE_TIME_SAFE 1" >>confdefs.h
+
+
 fi
 
 # gh-124228: While the libuuid library is available on NetBSD, it supports only UUID version 4.
@@ -14441,6 +14474,164 @@ then :
   have_uuid=no
 fi
 
+# gh-132710: The UUID node is fetched by using libuuid when possible
+# and cached. While the node is constant within the same process,
+# different interpreters may have different values as libuuid may
+# randomize the node value if the latter cannot be deduced.
+#
+# Consumers may define HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC
+# to indicate that libuuid is unstable and should not be relied
+# upon to deduce the MAC address.
+
+
+if test "$have_uuid" = "yes" -a "$HAVE_UUID_GENERATE_TIME_SAFE" = "1"
+then
+  { printf "%s\n" "$as_me:${as_lineno-$LINENO}: checking if uuid_generate_time_safe() node value is stable" >&5
+printf %s "checking if uuid_generate_time_safe() node value is stable... " >&6; }
+  save_CFLAGS=$CFLAGS
+save_CPPFLAGS=$CPPFLAGS
+save_LDFLAGS=$LDFLAGS
+save_LIBS=$LIBS
+
+
+  # Be sure to add the extra include path if we used pkg-config
+  # as HAVE_UUID_H may be set even though <uuid.h> is only reachable
+  # by adding extra -I flags.
+  #
+  # If the following script does not compile, we simply assume that
+  # libuuid is missing.
+  CFLAGS="$CFLAGS $LIBUUID_CFLAGS"
+  LIBS="$LIBS $LIBUUID_LIBS"
+  if test "$cross_compiling" = yes
+then :
+
+
+else case e in #(
+  e) cat confdefs.h - <<_ACEOF >conftest.$ac_ext
+/* end confdefs.h.  */
+
+    #include <inttypes.h>   // PRIu64
+    #include <stdint.h>     // uint64_t
+    #include <stdio.h>      // fopen(), fclose()
+
+    #ifdef HAVE_UUID_H
+    #include <uuid.h>
+    #else
+    #include <uuid/uuid.h>
+    #endif
+
+    #define ERR 1
+    int main(void) {
+        uuid_t uuid;  // unsigned char[16]
+        (void)uuid_generate_time_safe(uuid);
+        uint64_t node = 0;
+        for (size_t i = 0; i < 6; i++) {
+            node |= (uint64_t)uuid[15 - i] << (8 * i);
+        }
+        FILE *fp = fopen("conftest.out", "w");
+        if (fp == NULL) {
+            return ERR;
+        }
+        int rc = fprintf(fp, "%" PRIu64 "\n", node) >= 0;
+        rc |= fclose(fp);
+        return rc == 0 ? 0 : ERR;
+    }
+_ACEOF
+if ac_fn_c_try_run "$LINENO"
+then :
+
+      py_cv_uuid_node1=`cat conftest.out`
+
+fi
+rm -f core *.core core.conftest.* gmon.out bb.out conftest$ac_exeext \
+  conftest.$ac_objext conftest.beam conftest.$ac_ext ;;
+esac
+fi
+
+CFLAGS=$save_CFLAGS
+CPPFLAGS=$save_CPPFLAGS
+LDFLAGS=$save_LDFLAGS
+LIBS=$save_LIBS
+
+
+  save_CFLAGS=$CFLAGS
+save_CPPFLAGS=$CPPFLAGS
+save_LDFLAGS=$LDFLAGS
+save_LIBS=$LIBS
+
+
+  # Be sure to add the extra include path if we used pkg-config
+  # as HAVE_UUID_H may be set even though <uuid.h> is only reachable
+  # by adding extra -I flags.
+  #
+  # If the following script does not compile, we simply assume that
+  # libuuid is missing.
+  CFLAGS="$CFLAGS $LIBUUID_CFLAGS"
+  LIBS="$LIBS $LIBUUID_LIBS"
+  if test "$cross_compiling" = yes
+then :
+
+
+else case e in #(
+  e) cat confdefs.h - <<_ACEOF >conftest.$ac_ext
+/* end confdefs.h.  */
+
+    #include <inttypes.h>   // PRIu64
+    #include <stdint.h>     // uint64_t
+    #include <stdio.h>      // fopen(), fclose()
+
+    #ifdef HAVE_UUID_H
+    #include <uuid.h>
+    #else
+    #include <uuid/uuid.h>
+    #endif
+
+    #define ERR 1
+    int main(void) {
+        uuid_t uuid;  // unsigned char[16]
+        (void)uuid_generate_time_safe(uuid);
+        uint64_t node = 0;
+        for (size_t i = 0; i < 6; i++) {
+            node |= (uint64_t)uuid[15 - i] << (8 * i);
+        }
+        FILE *fp = fopen("conftest.out", "w");
+        if (fp == NULL) {
+            return ERR;
+        }
+        int rc = fprintf(fp, "%" PRIu64 "\n", node) >= 0;
+        rc |= fclose(fp);
+        return rc == 0 ? 0 : ERR;
+    }
+_ACEOF
+if ac_fn_c_try_run "$LINENO"
+then :
+
+      py_cv_uuid_node2=`cat conftest.out`
+
+fi
+rm -f core *.core core.conftest.* gmon.out bb.out conftest$ac_exeext \
+  conftest.$ac_objext conftest.beam conftest.$ac_ext ;;
+esac
+fi
+
+CFLAGS=$save_CFLAGS
+CPPFLAGS=$save_CPPFLAGS
+LDFLAGS=$save_LDFLAGS
+LIBS=$save_LIBS
+
+
+  if test -n "$py_cv_uuid_node1" -a "$py_cv_uuid_node1" = "$py_cv_uuid_node2"
+  then
+    printf "%s\n" "#define HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC 1" >>confdefs.h
+
+    { printf "%s\n" "$as_me:${as_lineno-$LINENO}: result: stable" >&5
+printf "%s\n" "stable" >&6; }
+  else
+    { printf "%s\n" "$as_me:${as_lineno-$LINENO}: result: unstable" >&5
+printf "%s\n" "unstable" >&6; }
+  fi
+fi
+
 # 'Real Time' functions on Solaris
 # posix4 on Solaris 2.6
 # pthread (first!) on Linux
diff --git a/configure.ac b/configure.ac
index 1aedd54bd0c70d..7f4328e66cdc5c 100644
--- a/configure.ac
+++ b/configure.ac
@@ -3714,15 +3714,17 @@ dnl check for uuid dependencies
 AH_TEMPLATE([HAVE_UUID_H], [Define to 1 if you have the <uuid.h> header file.])
 AH_TEMPLATE([HAVE_UUID_UUID_H], [Define to 1 if you have the <uuid/uuid.h> header file.])
 AH_TEMPLATE([HAVE_UUID_GENERATE_TIME_SAFE], [Define if uuid_generate_time_safe() exists.])
+AH_TEMPLATE([HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC], [Define if uuid_generate_time_safe() is able to deduce a MAC address.])
 have_uuid=missing
 
 dnl AIX provides support for RFC4122 (uuid) in libc.a starting with AIX 6.1
 dnl (anno 2007). FreeBSD and OpenBSD provides support in libc as well.
 dnl Little-endian FreeBSD, OpenBSD and NetBSD needs encoding into an octet
 dnl stream in big-endian byte-order
-AC_CHECK_HEADERS([uuid.h],
-  [AC_CHECK_FUNCS([uuid_create uuid_enc_be],
-    [have_uuid=yes
+AC_CHECK_HEADERS([uuid.h], [
+  AC_CHECK_FUNCS([uuid_create uuid_enc_be], [
+    have_uuid=yes
+    ac_cv_have_uuid_h=yes
     LIBUUID_CFLAGS=${LIBUUID_CFLAGS-""}
     LIBUUID_LIBS=${LIBUUID_LIBS-""}
   ])
@@ -3732,19 +3734,29 @@ AS_VAR_IF([have_uuid], [missing], [
   PKG_CHECK_MODULES(
     [LIBUUID], [uuid >= 2.20],
       [dnl linux-util's libuuid has uuid_generate_time_safe() since v2.20 (2011)
-      dnl and provides <uuid.h>.
+      dnl and provides <uuid.h> assuming specific include paths are given
       have_uuid=yes
-      AC_DEFINE([HAVE_UUID_H], [1])
-      AC_DEFINE([HAVE_UUID_GENERATE_TIME_SAFE], [1])
+      ac_cv_have_uuid_generate_time_safe=yes
+      # The uuid.h file to include may be <uuid.h> *or* <uuid/uuid.h>.
+      # Since pkg-config --cflags uuid may return -I/usr/include/uuid,
+      # it's possible to write '#include <uuid.h>' in _uuidmodule.c,
+      # assuming that the compiler flags are properly updated.
+      #
+      # Ideally, we should have defined HAVE_UUID_H if and only if
+      # #include <uuid.h> can be written, *without* assuming extra
+      # include path.
+      ac_cv_have_uuid_h=yes
     ], [
       WITH_SAVE_ENV([
         CPPFLAGS="$CPPFLAGS $LIBUUID_CFLAGS"
         LIBS="$LIBS $LIBUUID_LIBS"
         AC_CHECK_HEADERS([uuid/uuid.h], [
+          ac_cv_have_uuid_uuid_h=yes
           PY_CHECK_LIB([uuid], [uuid_generate_time], [have_uuid=yes])
-          PY_CHECK_LIB([uuid], [uuid_generate_time_safe],
-            [have_uuid=yes
-            AC_DEFINE([HAVE_UUID_GENERATE_TIME_SAFE], [1]) ]) ])
+          PY_CHECK_LIB([uuid], [uuid_generate_time_safe], [
+            have_uuid=yes
+            ac_cv_have_uuid_generate_time_safe=yes
+          ])])
         AS_VAR_IF([have_uuid], [yes], [
           LIBUUID_CFLAGS=${LIBUUID_CFLAGS-""}
           LIBUUID_LIBS=${LIBUUID_LIBS-"-luuid"}
@@ -3759,12 +3771,19 @@ AS_VAR_IF([have_uuid], [missing], [
   AC_CHECK_HEADERS([uuid/uuid.h], [
     AC_CHECK_FUNC([uuid_generate_time], [
       have_uuid=yes
+      ac_cv_have_uuid_uuid_h=yes
       LIBUUID_CFLAGS=${LIBUUID_CFLAGS-""}
       LIBUUID_LIBS=${LIBUUID_LIBS-""}
     ])
   ])
 ])
 
+AS_VAR_IF([ac_cv_have_uuid_h], [yes], [AC_DEFINE([HAVE_UUID_H], [1])])
+AS_VAR_IF([ac_cv_have_uuid_uuid_h], [yes], [AC_DEFINE([HAVE_UUID_UUID_H], [1])])
+AS_VAR_IF([ac_cv_have_uuid_generate_time_safe], [yes], [
+  AC_DEFINE([HAVE_UUID_GENERATE_TIME_SAFE], [1])
+])
+
 # gh-124228: While the libuuid library is available on NetBSD, it supports only UUID version 4.
 # This restriction inhibits the proper generation of time-based UUIDs.
 if test "$ac_sys_system" = "NetBSD"; then
@@ -3774,6 +3793,68 @@ fi
 
 AS_VAR_IF([have_uuid], [missing], [have_uuid=no])
 
+# gh-132710: The UUID node is fetched by using libuuid when possible
+# and cached. While the node is constant within the same process,
+# different interpreters may have different values as libuuid may
+# randomize the node value if the latter cannot be deduced.
+#
+# Consumers may define HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC
+# to indicate that libuuid is unstable and should not be relied
+# upon to deduce the MAC address.
+AC_DEFUN([PY_EXTRACT_UUID_GENERATE_TIME_SAFE_MAC], [WITH_SAVE_ENV([
+  # Be sure to add the extra include path if we used pkg-config
+  # as HAVE_UUID_H may be set even though <uuid.h> is only reachable
+  # by adding extra -I flags.
+  #
+  # If the following script does not compile, we simply assume that
+  # libuuid is missing.
+  CFLAGS="$CFLAGS $LIBUUID_CFLAGS"
+  LIBS="$LIBS $LIBUUID_LIBS"
+  AC_RUN_IFELSE([AC_LANG_SOURCE([[
+    #include <inttypes.h>   // PRIu64
+    #include <stdint.h>     // uint64_t
+    #include <stdio.h>      // fopen(), fclose()
+
+    #ifdef HAVE_UUID_H
+    #include <uuid.h>
+    #else
+    #include <uuid/uuid.h>
+    #endif
+
+    #define ERR 1
+    int main(void) {
+        uuid_t uuid;  // unsigned char[16]
+        (void)uuid_generate_time_safe(uuid);
+        uint64_t node = 0;
+        for (size_t i = 0; i < 6; i++) {
+            node |= (uint64_t)uuid[15 - i] << (8 * i);
+        }
+        FILE *fp = fopen("conftest.out", "w");
+        if (fp == NULL) {
+            return ERR;
+        }
+        int rc = fprintf(fp, "%" PRIu64 "\n", node) >= 0;
+        rc |= fclose(fp);
+        return rc == 0 ? 0 : ERR;
+    }]])], [
+      AS_VAR_SET([$1], [`cat conftest.out`])
+    ], [], []
+  )])])
+
+if test "$have_uuid" = "yes" -a "$HAVE_UUID_GENERATE_TIME_SAFE" = "1"
+then
+  AC_MSG_CHECKING([if uuid_generate_time_safe() node value is stable])
+  PY_EXTRACT_UUID_GENERATE_TIME_SAFE_MAC([py_cv_uuid_node1])
+  PY_EXTRACT_UUID_GENERATE_TIME_SAFE_MAC([py_cv_uuid_node2])
+  if test -n "$py_cv_uuid_node1" -a "$py_cv_uuid_node1" = "$py_cv_uuid_node2"
+  then
+    AC_DEFINE([HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC], [1])
+    AC_MSG_RESULT([stable])
+  else
+    AC_MSG_RESULT([unstable])
+  fi
+fi
+
 # 'Real Time' functions on Solaris
 # posix4 on Solaris 2.6
 # pthread (first!) on Linux
diff --git a/pyconfig.h.in b/pyconfig.h.in
index c8a0174bd38aee..638d8c81656bd0 100644
--- a/pyconfig.h.in
+++ b/pyconfig.h.in
@@ -1587,6 +1587,9 @@
 /* Define if uuid_generate_time_safe() exists. */
 #undef HAVE_UUID_GENERATE_TIME_SAFE
 
+/* Define if uuid_generate_time_safe() is able to deduce a MAC address. */
+#undef HAVE_UUID_GENERATE_TIME_SAFE_STABLE_MAC
+
 /* Define to 1 if you have the <uuid.h> header file. */
 #undef HAVE_UUID_H