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Cruella de Vil is the main antagonist of The Hundred and One Dalmatians, a 1956 novel penned by Dodie Smith which served as basis for Disney's 101 Dalmatians media franchise, which encompasses two animated films (the 1961 theatrical version and its 2003 direct-to-video sequel), two live-action films (the 1996 theatrical remake and its 2000 sequel 102 Dalmatians), a 1997 animated TV series, and various video games. Betty Lou Gerson voiced Cruella in the 1961 cartoon movie, while Glenn Close portrayed her in both live-action adaptations.

She also makes an appearance on ABC's live-action drama Once Upon a Time, where Victoria Smurfit plays her role.