diff --git a/cmake/CMakeLists.txt b/cmake/CMakeLists.txt
index 85e8e40dfd..40773cd8fd 100644
--- a/cmake/CMakeLists.txt
+++ b/cmake/CMakeLists.txt
@@ -109,10 +109,11 @@ option(onnxruntime_USE_ROCM "Build with AMD GPU support" OFF)
 option(onnxruntime_DISABLE_CONTRIB_OPS "Disable contrib ops" OFF)
 option(onnxruntime_DISABLE_ML_OPS "Disable traditional ML ops" OFF)
 option(onnxruntime_DISABLE_SPARSE_TENSORS "Disable sparse tensors data types" OFF)
+option(onnxruntime_MINIMAL_BUILD "Exclude as much as possible from the build. Support ORT format models. No support for ONNX format models." OFF)
 cmake_dependent_option(onnxruntime_DISABLE_RTTI "Disable RTTI" ON "onnxruntime_MINIMAL_BUILD;NOT onnxruntime_ENABLE_PYTHON" OFF)
 # For now onnxruntime_DISABLE_EXCEPTIONS will only work with onnxruntime_MINIMAL_BUILD, more changes (ONNX, non-CPU EP, ...) are required to run this standalone
-option(onnxruntime_DISABLE_EXCEPTIONS "Disable exception handling. Requires onnxruntime_MINIMAL_BUILD currently." OFF)
-option(onnxruntime_MINIMAL_BUILD "Exclude as much as possible from the build. Support ORT format models. No support for ONNX format models." OFF)
+cmake_dependent_option(onnxruntime_DISABLE_EXCEPTIONS "Disable exception handling. Requires onnxruntime_MINIMAL_BUILD currently." ON "onnxruntime_MINIMAL_BUILD;NOT onnxruntime_ENABLE_PYTHON" OFF)
+
 option(onnxruntime_EXTENDED_MINIMAL_BUILD "onnxruntime_MINIMAL_BUILD with support for execution providers that compile kernels." OFF)
 option(onnxruntime_MINIMAL_BUILD_CUSTOM_OPS "Add custom operator kernels support to a minimal build." OFF)
 option(onnxruntime_REDUCED_OPS_BUILD "Reduced set of kernels are registered in build via modification of the kernel registration source files." OFF)
@@ -406,7 +407,7 @@ if (onnxruntime_DISABLE_EXTERNAL_INITIALIZERS)
 endif()
 
 if (onnxruntime_DISABLE_RTTI)
-  add_compile_definitions(ORT_NO_RTTI GOOGLE_PROTOBUF_NO_RTTI)
+  add_compile_definitions(ORT_NO_RTTI)
   if (MSVC)
     # Disable RTTI and turn usage of dynamic_cast and typeid into errors
     add_compile_options("$<$<COMPILE_LANGUAGE:CXX>:/GR->" "$<$<COMPILE_LANGUAGE:CXX>:/we4541>")
@@ -428,6 +429,10 @@ if (onnxruntime_DISABLE_EXCEPTIONS)
     message(FATAL_ERROR "onnxruntime_MINIMAL_BUILD required for onnxruntime_DISABLE_EXCEPTIONS")
   endif()
 
+  if (onnxruntime_ENABLE_PYTHON)
+    # pybind11 highly depends on C++ exceptions.
+    message(FATAL_ERROR "onnxruntime_ENABLE_PYTHON must be disabled for onnxruntime_DISABLE_EXCEPTIONS")
+  endif()
   add_compile_definitions("ORT_NO_EXCEPTIONS")
   add_compile_definitions("MLAS_NO_EXCEPTION")
   add_compile_definitions("ONNX_NO_EXCEPTIONS")
@@ -760,7 +765,7 @@ else()
     set(protobuf_WITH_ZLIB OFF CACHE BOOL "Build with zlib support" FORCE)
   endif()
   if (onnxruntime_DISABLE_RTTI)
-    set(protobuf_DISABLE_RTTI OFF CACHE BOOL "Remove runtime type information in the binaries" FORCE)
+    set(protobuf_DISABLE_RTTI ON CACHE BOOL "Remove runtime type information in the binaries" FORCE)
   endif()
   add_subdirectory(${PROJECT_SOURCE_DIR}/external/protobuf/cmake EXCLUDE_FROM_ALL)