A notable downside that is not mentioned: the Python interpreter is far from Valgrind-clean. Valgrind is generally a powerful tool for debugging memory errors, but if you wrap your C code in Python, Valgrind will be so noisy as to be ineffective. Python startup is also very heavyweight; combined with the ~60x slowdown from Valgrind this is something you are going to notice.

The Python interpreter does not even use malloc()/free() directly by default; it layers its own memory allocator on top called PyMalloc (https://docs.python.org/3/c-api/memory.html#pymalloc). You can disable this by setting an environment variable (PYTHONMALLOC=malloc), but even then you will see many Valgrind warnings inside the Python interpreter itself.