In 2010, de Rossi published her autobiography, titled Unbearable Lightness: A Story of Loss and Gain, in whose pages she wrote about the turmoil that she had experienced in her life, including suffering from anorexia nervosa and bulimia and being misdiagnosed with lupus.
To promote the book, she appeared on The Oprah Winfrey Show and The Ellen De Generes Show.
She ranked 69th in Stuff Magazine's 100 Sexiest Women, 31 in Femme Fatales' Sexiest Women of 2003 list, and 24 in Maxim's 100 Sexiest Women List in 2004; in late 2006, the magazine Blender listed her as one of the hottest women of film and TV.
She declined to publicly discuss the relationship or her sexual orientation at the time.
De Rossi and Gregorini broke up in late 2004 because de Rossi began dating De Generes, whom she met backstage at an awards show.
TV Guide included her and Ellen De Generes in their Power A-List couples in 2007.
In February 2012, it was announced that ABC had ordered a pilot for a new drama series The Smart One, one of whose executive producers was listed as Ellen De Generes, and which featured de Rossi in a leading role.
In April 2017, in season six, de Rossi's character, Elizabeth North, was killed off by a golf club attack.