In 1999 she co-starred in Will Smith's big-budget Wild Wild West, and played a supporting role in Kevin Smith's Dogma.
Around 2000, Hayek founded film production company Ventanarosa, through which she produces film and television projects.
In the Time of the Butterflies is a 2001 feature film based on the Julia Álvarez book of the same name, covering the lives of the Mirabal sisters.
She has been in 10 celebrity relationships averaging approximately 6.1 years each.
Hayek guest-starred on Ugly Betty as Sofia Reyes, a magazine editor.
She also had a cameo playing an actress in the telenovela within the show.
Her first feature as a producer was 1999's El Coronel No Tiene Quien Le Escriba, Mexico's official selection for submission for Best Foreign Film at the Oscars. Starring Hayek as Frida Kahlo, and Alfred Molina as her unfaithful husband, Diego Rivera, the film was directed by Julie Taymor and featured an entourage of stars in supporting and minor roles (Valeria Golino, Ashley Judd, Edward Norton, Geoffrey Rush) and cameos (Antonio Banderas).
She earned a Best Actress Academy Award nomination for her performance.