In 1978, Struycken was “discovered” as an actor at the corner of Hollywood and Vine in Los Angeles by a woman who had abandoned her car in the middle of the street, calling after him: “We need you for a movie!”. The film was Sgt. Pepper’s Lonely Hearts Club Band.

Struycken played Terak in the 1985 TV film Ewoks: The Battle for Endor, a spin-off to the original Star Wars trilogy.

Struycken appeared as Fidel, Jack Nicholson’s manservant, in the 1987 film The Witches of Eastwick. That same year, he appeared as Mr. Homn in “Haven”, an episode of the television series Star Trek: The Next Generation, a role he would reprise in four more episodes until 1992.

In 1991, he starred as butler Lurch in the feature film The Addams Family. He reprised the role in the 1993 sequel, Addams Family Values, and the TV movie Addams Family Reunion. Director Barry Sonnenfeld also picked Struycken for a small role in Men in Black.

Struycken collaborated on several projects with writer and director Rene Daalder, including the 1986 punk rock musical Population: 1, which featured Tomata du Plenty, of The Screamers, and which was released on DVD in October 2008.

He portrayed the mystical guide-character “The Giant” in David Lynch and Mark Frost’s hit 1990–91 ABC television series Twin Peaks. He also appears in the 2017 sequel series, Twin Peaks: The Return. He appears as the “Moonlight Man” in the 2017 Netflix original movie Gerald’s Game.