Simon, 58, recently announced he was diagnosed with terminal cancer and has only months to live. He is twice-divorced and has no children.
Although he left "The Simpsons" in 1993, he retained an executive-producer credit that still earns him "tens of millions" of dollars annually, he told The Hollywood Reporter.
The show-runner of "Taxi" when he was just 24 says, "I don't know," when asked to estimate his charitable donations to date.
He founded the $23 million Malibu-based Sam Simon Foundation, which offers vegan food to hungry people, and rescues stray dogs, the entertainment industry trade newspaper said.
Simon also is a supporter of PETA, which named its Norfolk, Va., headquarters the Sam Simon Center, and he made substantial donations to Save the Children and Sea Shepherd Conservation Society organizations, as well, The Hollywood Reporter said.
It said he has made contributions to non-profit groups for years and has stepped up his charity funding since he became ill.
"I think it's really nice for him that he's doing it now and he gets to see the results of his philanthropy," his ex-wife Jennifer Tilly said. "He really does have a passion to survive, and the longer he's on the Earth, the more good work he can do."
"The sort of lifetime achievement stuff that I'm getting now is kind of like Tom Sawyer's funeral because they all know I'm sick. I am getting buildings named after me and awards and stuff. The truth is, I have more money than I'm interested in spending. Everyone in my family is taken care of. And I enjoy this," Simon told the newspaper.