Leguizamo also starred in Romeo + Juliet as Tybalt Capulet, as Violator in Spawn, Cholo in Land of the Dead, and Pestario 'Pest' Vargas in The Pest, the latter being one of his few roles as a lead actor in a studio film. In 1995, he starred as drag queen Chi-Chi Rodriguez in To Wong Foo, Thanks for Everything! Julie Newmar for which he received a Golden Globe Nomination for Best Supporting Actor, and starred in the 1996 action film Executive Decision as Captain Rat. In 2002, he starred in the movie Empire. To promote the 2001 movie Moulin Rouge!, he appeared on a celebrity edition of the US version of Who Wants to Be a Millionaire? with Kelly Ripa, Kevin Sorbo, Alfre Woodard, Martin Short and Chevy Chase. Appearing as the first celebrity to sit in the hot seat, he eventually tried for $125,000, but got the answer wrong. Later in 2002, on the syndicated version, a question about the movie featured his character and Meredith Vieira mentioned that Leguizamo had played Lautrec and had been on the show.
In 1995 Leguizamo created, produced, wrote, and starred in the 1995 Latino-oriented variety show called House of Buggin' on Fox Television. Some audiences saw this as the Latino version of In Living Color. The show showcased Leguizamo's well-known ability to assume a wide variety of colorful, energetic characters, but due to poor ratings the show ran less than one season.