Valletta has acted in several films, been on the cover of magazines and in advertisements for Louis Vuitton, Calvin Klein and Versace and hosted MTV's House of Style with friend and fellow supermodel Shalom Harlow.

Valletta was scheduled to appear on Punk'd on Season 6 Episode 3, along with David Boreanaz and Kristin Cavallari, but Kutcher had to move the prank played on Valletta to an episode later to make room for the prank played on Dallas Cowboys wide receiver Terrell Owens, which is based on his suspension on November 19, 2005, while playing for the Philadelphia Eagles.

Valletta is married to renowned Olympic volleyball player Christian "Chip" McCaw, with whom she has a son, Auden. Before her marriage, she dated Leonardo Dicaprio in early 1998. As of August 24, 2006, her publicist announced that she was going into rehab for non-substance abuse issues related to stress and image problems.

Valletta also serves as the spokesperson for Oceana's Seafood Contamination Campaign, where she brings awareness of the dangers of mercury poisoning in various kinds of seafood. The decision to join Oceana's campaign was prompted by the mercury-poisoning experience of a friend and the fact that she is a mother.

In August 2006, the New York Daily News reported that Valletta completed a stint at The Meadow rehabilitation facility in Wickenburg, Arizona, for stress and non-substance-related issues. Valletta told People magazine, "As was correctly reported earlier this week, my stay at The Meadows had nothing to do with substance abuse or addiction; I am pleased to say I have seven years' sobriety. But I continue every day to heal and grow as a person".