diff --git a/Include/pymacconfig.h b/Include/pymacconfig.h
index 806e41955efd7f..615abe103ca038 100644
--- a/Include/pymacconfig.h
+++ b/Include/pymacconfig.h
@@ -7,7 +7,9 @@
 #define PY_MACCONFIG_H
 #ifdef __APPLE__
 
+#undef ALIGNOF_MAX_ALIGN_T
 #undef SIZEOF_LONG
+#undef SIZEOF_LONG_DOUBLE
 #undef SIZEOF_PTHREAD_T
 #undef SIZEOF_SIZE_T
 #undef SIZEOF_TIME_T
@@ -20,6 +22,7 @@
 #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__)
@@ -74,8 +77,14 @@
 #  define DOUBLE_IS_LITTLE_ENDIAN_IEEE754
 #endif
 
-#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
 
 #endif   // __APPLE__
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.