The show is to premiere in December on Netflix.
The casting announcement was made Wednesday at France's Annecy Animation Festival during a career-retrospective discussion with del Toro.
"Trollhunters features a tale of two fantastical worlds set to collide in an epic saga," a press release explained. "Set in the fictional suburb of Arcadia, our unlikely hero, Jim, and his two best friends make a startling discovery that beneath their hometown lies a hidden battle between good trolls and bad, the outcome of which will impact their lives forever."
Perlman and del Toro have also collaborated on the films Hellboy and Pacific Rim.