The actor - who currently appears in Showtime's Homeland - told New York Magazine that joining the violent CBS drama in 2005 was the "biggest public mistake I ever made".
"I thought [the show] was something very different," said Patinkin, who left Criminal Minds after two seasons in 2007. "I never thought they were going to kill and rape all these women 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."
However, the 59-year-old Princess Bride star defended the violence in his current show Homeland, on which he plays CIA operative Saul.
"I'm not making a judgment on the taste [of people who watch crime procedurals]," he insisted. "But I'm concerned about the effect it has. Audiences all over the world use this programming as their bedtime story. This isn't what you need to be dreaming about.
"A show like Homeland is the antidote. It asks why there's a need for violence in the first place."
Criminal Minds enters its eighth season on September 26, on CBS in the US. The series airs on Sky Living in the UK.