McDonald, who has commuted between New York and Los Angeles over the past four years, may still appear on the ABC series as a guest star.
"I have spent four amazing years working with the best cast and crew on television at Private Practice," McDonald told TVLine.com, which first reported her departure. "Though I am stepping away from the series as a regular in order to spend more time in New York with my family, I am not closing the door on Private Practice or the character, Naomi. I am beyond grateful to Shonda Rhimes, ABC, and the team behind the show."
The Tony-winning actress is the second series regular to leave the ABC medical drama following the death of Chris Lowell's character, Dell, in the Season 3 finale.
Private Practice airs Thursdays at 10/9c.