The couple have chosen to end their marriage after being wed for more than 30 years, Entertainment Tonight reports.
The news was confirmed by the duo's spokesperson Stan Rosenfield.
DeVito and Perlman married in January 1982 and the couple have three children - Lucy, Grace and Jacob.
DeVito recently criticised the spate of movie remakes, claiming that they have "stunk", but he is believed to be working on a sequel to his movie Twins with Arnold Schwarzenegger.
Meanwhile, Perlman - who is probably best known for her role in Cheers - recently guest starred in an episode of Hot In Cleveland and worked on an ABC pilot earlier this year with Kirstie Alley which was ultimately not picked up.
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