Leoni had lead roles in films such as Deep Impact (1998), The Family Man (2000), Jurassic Park III (2001), Spanglish (2004), and Fun with Dick and Jane (2005).

Her mother, Emily Ann (née Patterson),[2][3] was a dietitian and nutritionist, and her father, Anthony Pantaleoni, was a corporate lawyer with the firm Fulbright & Jaworski.

[5][6][7] Leoni's paternal grandmother, American silent film actress and humanitarian Helenka Adamowska Pantaleoni, was born in Brookline, Massachusetts to Polish musicians Józef Adamowski and Antonina Szumowska-Adamowska.

[10] In a 2017 episode of Finding Your Roots, hosted by Henry Louis Gates Jr., Leoni discovered that her mother Emily, who was adopted, is the biological daughter of Mavis Abilene Gindratt from Vick, Louisiana, and Sumpter James Daniel, whose ancestors originated in Ireland.

Later in that year, she landed the lead role in the ABC/NBC sitcom The Naked Truth, playing Nora Wilde, a tabloid news journalist.

Leoni had the female lead role in the 1995 action comedy film Bad Boys, which was a box office success, grossing over $141 million worldwide.

[16] After leaving television, Leoni had a leading role in Deep Impact (1998), a big-budget disaster film featuring projected effects of a comet hurtling towards Earth.

[17] She later had main roles in two other big budget movies: romantic comedy The Family Man (2000), co-starring alongside Nicolas Cage, and science fiction film Jurassic Park III (2001) as William H. Macy's character's ex-wife.

In 2002, she starred as a film studio executive in Hollywood Ending, directed by Woody Allen and had a supporting role in the box office bomb crime drama People I Know.

[20] Leoni married Neil Joseph Tardio Jr., a television commercial producer, on June 8, 1991, at St. Luke's Episcopal Church in Hope Township, New Jersey.