Kelly Kamalelehua Smith (the middle name "Kamalelehua" means 'garden of lehuas' in Hawaiian - a lehua being a well known Hawaiian flower) was born in Honolulu, Hawaii. Her mother Linda, was an administrator of a mental health center and her father, who worked for an agricultural firm, drowned when Preston was only three years old. Her mother married Peter Palzis, a personnel director, who subsequently adopted her; she used his name when she first began her acting career until 1984. She has a younger half-brother, Chris Palzis. As a child, she spent time living in Iraq and also in Australia, where she attended Pembroke School in Adelaide. She went on to Punahou School and studied drama and theater at the University of Southern California.
While living in Australia, Preston was discovered at 16 by a fashion photographer who helped her get work in commercials and other small parts, and organized Preston's first film audition in 1980 for the role of Emmeline in The Blue Lagoon (1980), which she lost to the younger Brooke Shields. At that time she changed her last name to Preston.
Her first prominent film roles came in 1985, firstly as Marilyn McCauley in romantic comedy teen flick Mischief and then as the beautiful but shallow Deborah Ann Fimple in another teen romantic comedy, Secret Admirer. Other notable roles included SpaceCamp (1986), Twins (1988) with Arnold Schwarzenegger and Danny DeVito, Avery Bishop in Jerry Maguire (1996) with Tom Cruise, Jane Aubrey in For Love of the Game with Kevin Costner and Kate Newell in Holy Man (1998) with Eddie Murphy and Jeff Goldblum.
She played the girlfriend of her husband, John Travolta's, character "Terl" in the 2000 film Battlefield Earth, and received "Worst Supporting Actress" at the 21st Golden Raspberry Awards for her role in the film. In 2005 she appeared as the flying, superheroine mother of the protagonist in the film Sky High.
Preston was featured in the chart-topping Maroon 5 music video "She Will Be Loved" in 2004. The video features a love triangle and romantic scenes between Preston and Maroon 5 frontman Adam Levine. In 2008, she was cast in a television pilot for a potential show called Suburban Shootout. She had a short term recurring role on Medium.
In 2008, Preston starred in the Lifetime movie The Tenth Circle, directed by Peter Markle. The film was shot in Nova Scotia and featured Ron Eldard, Brittany Robertson, Michael Riley, Jamie Johnston and Geordie Brown.
She is a spokeswoman for Neutrogena since 2005 and appears in print and television advertisements.
Preston was married to actor Kevin Gage from 1985 until their divorce in 1987. She also had a relationship with George Clooney, who gave her Max, a pet pig that he kept after the couple split up. She was briefly engaged to Charlie Sheen in 1990, but ended the relationship shortly after he accidentally shot her in the arm.
Preston first met John Travolta in 1987 while filming The Experts. They married in 1991, traveling to Paris on an Air France Concorde for a wedding ceremony at the Hotel de Crillon (close to Place de la Concorde) on September 5, 1991. However, a second ceremony was required because the first, performed by a French Scientology minister (both Preston and Travolta are Scientologists), was considered invalid. This second ceremony took place on September 12 in Daytona Beach, Florida. They had three children: son Jett (April 13, 1992 – January 2, 2009), daughter Ella Bleu (born 2000), and son Benjamin (born 2010).
Preston's son Jett Travolta was described as suffering from Kawasaki disease as an infant and had a history of seizures. In 2003, Preston appeared on the Montel Williams show to promote L. Ron Hubbard's Purification Rundown, which she credited with helping her son.
On January 2, 2009, Jett Travolta died while the family was on a holiday vacation in The Bahamas. His death was attributed to a seizure. In September 2009, Travolta and Preston confirmed longstanding speculations when they testified that their son had autism and suffered regular seizures. This revelation came during their testimony at the trial resulting from an extortion attempt related to their son's death.
On January 23, 2009, three people were arrested in the Bahamas in connection with a multimillion-dollar extortion plot against Travolta and Preston concerning the circumstances of their son's death. One of the men, Obie Wilchcombe, a member of the Bahamian Parliament and former Bahamian Minister of Tourism, was described as a "close friend" of Travolta and Preston. Two others allegedly involved were an EMT named Tarino Lightbourne and a Bahamian senator named Pleasant Bridgewater. Bridgewater was charged with abetment to extort and conspiracy to extort and resigned from the Senate as a result of the allegations.