Mitchell began a longtime romantic relationship with Eddie Murphy after meeting him in 1988 at an NAACP Image Awards show. They lived together for almost two years before getting married at the Grand Ballroom of The Plaza Hotel in New York City on March 18, 1993. Together they have 4 daughters and 1 son: Bria, son Myles, Shayne, Zola, and Bella. In August 2005, Mitchell filed for divorce, citing "irreconcilable differences". The divorce was finalized on April 17, 2006.
In June 2009, Nicole's partner was Michael Strahan, a retired American NFL player. In August 2014, Michael and Nicole called it quits, owing to busy schedules.
