Producers of the Fox animated comedy confirmed to Entertainment Weekly that the Hollywood star will have a brief voiceover guest slot in a cutaway gag.
© Rex Features
© Fox
Family Guy
"When [Johnny] was in the booth, he said that he felt like he hadn't done that voice since he did it in front of the camera," said Family Guy exec Mark Hentemann.
"He was able to snap right back into Edward Scissorhands once we pulled up a clip from the movie.
"He was amazing - and demonstrated extraordinary patience with all the fawning women in our office who swarmed him."
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Previous guest stars on Family Guy have included Robert Downey Jr, Kiefer Sutherland, Ricky Gervais, Neil Patrick Harris and Mick Jagger.
Family Guy returns to Fox in the US for an 11th season on September 30.
Watch Depp as Edward Scissorhands trying to eat dinner below:
