diff --git a/Include/pymacconfig.h b/Include/pymacconfig.h
index 00459a03b980be..e7fdb5506daa1e 100644
--- a/Include/pymacconfig.h
+++ b/Include/pymacconfig.h
@@ -8,9 +8,10 @@
       * only compile-time constant in these scenarios.
       */
 
-#if defined(__APPLE__)
+#ifdef __APPLE__
 
 # undef SIZEOF_LONG
+# undef SIZEOF_LONG_DOUBLE
 # undef SIZEOF_PTHREAD_T
 # undef SIZEOF_SIZE_T
 # undef SIZEOF_TIME_T
@@ -23,6 +24,7 @@
 # undef DOUBLE_IS_BIG_ENDIAN_IEEE754
 # undef DOUBLE_IS_LITTLE_ENDIAN_IEEE754
 # undef HAVE_GCC_ASM_FOR_X87
+# undef HAVE_GCC_ASM_FOR_X64
 
 #    undef VA_LIST_IS_ARRAY
 #    if defined(__LP64__) && defined(__x86_64__)
@@ -80,8 +82,14 @@
 #define DOUBLE_IS_LITTLE_ENDIAN_IEEE754
 #endif /* __BIG_ENDIAN */
 
-#ifdef __i386__
+#if defined(__i386__) || defined(__x86_64__)
 # define HAVE_GCC_ASM_FOR_X87
+# define ALIGNOF_MAX_ALIGN_T 16
+# define HAVE_GCC_ASM_FOR_X64 1
+# define SIZEOF_LONG_DOUBLE 16
+#else
+# define ALIGNOF_MAX_ALIGN_T 8
+# define SIZEOF_LONG_DOUBLE 8
 #endif
 
 
diff --git a/Misc/NEWS.d/next/macOS/2023-12-07-14-19-46.gh-issue-110820.DIxb_F.rst b/Misc/NEWS.d/next/macOS/2023-12-07-14-19-46.gh-issue-110820.DIxb_F.rst
new file mode 100644
index 00000000000000..0badace7928745
--- /dev/null
+++ b/Misc/NEWS.d/next/macOS/2023-12-07-14-19-46.gh-issue-110820.DIxb_F.rst
@@ -0,0 +1,3 @@
+Make sure the preprocessor definitions for ``ALIGNOF_MAX_ALIGN_T``,
+``SIZEOF_LONG_DOUBLE`` and ``HAVE_GCC_ASM_FOR_X64`` are correct for
+Universal 2 builds on macOS.