Nichols was born in the Rogers Park neighborhood of Chicago, Illinois, to a father of Romanian and Hungarian descent and a Texan mother of Spanish and Mexican ancestry. She was raised in Naperville, Illinois. She is the oldest of three siblings, having two younger brothers. A rebellious teenager, Nichols stated in an interview with AskMen.com, "I remember being 17 and looking around at some of the people that I was hanging out with, and I had this realization that if I didn’t knock this off now it would become my life", and replaced her rebellious behavior with more productive activities like acting.

Nichols, a Scientologist, is an active advocate of Criminon and the Citizens Commission on Human Rights. She became a member of Church of Scientology when she was introduced to it by her chiropractor. She currently resides in Los Angeles, California.

She is also known for her portrayal of Audrey Griswold in Vegas Vacation and for being the spokesperson for Bally Total Fitness. Nichols will also portray Sarah Monahan in the supernatural crime drama series The Gates.

Marisol married Taron Lexton on April 13, 2008. They welcomed their first child Rain India Lexton, born September 30, 2008.