The star played a criminal profiler in the programme for two seasons, but quit before work started on the third series.
Patinkin now reveals he couldn't stand the gory storylines and wishes he had never taken the job.
He tells New York Magazine, "The biggest public mistake I ever made was that I chose to do Criminal Minds in the first place. I thought it was something very different. I never thought they were going to kill and rape all these women (in storylines) every night, every day, week after week, year after year... It was very destructive to my soul and my personality. After that, I didn't think I would get to work in television again."
Patinkin went on to land a role in hit drama Homeland opposite Claire Danes, and he is much happier in his new job.
He adds, "A show like Homeland is the antidote. It asks why there's a need for violence in the first place."