A former high school cheerleader, Carlisle is also the eldest of seven children. In 1986, Carlisle married Morgan Mason, son of the British actor James Mason, and former Deputy United States Chief of Protocol. Morgan made appearances in Carlisle's videos "Mad About You," and "Heaven Is a Place on Earth". They have a son, James Duke Mason (born April 27, 1992).

She has been reported as being "deeply into Buddhist chanting," though precisely what form is unclear. In an interview, printed on March 7, 2007, the singer stated that: "I was wondering about happiness and started reading a lot of books by the Dalai Lama, and slowly embraced Buddhism" (published by Newindpress, India). On Sydney Morning Herald: "I don't smoke anymore, I don't drink any more and I don't do drugs any more. I am very much into my Buddhism. I found turning 40 a real passage in time for me".

She appeared nude for the cover feature of the August 2001 Playboy, around the time of the Go-Go's definitive