May-Treanor is the daughter of Bob "Butch" May, a member of the 1968 US volleyball team and prominent beach player, and Barbara May, a nationally-ranked tennis player who later transitioned to beach volleyball. Barbara died of cancer in 2002. A prominent tattoo on Misty's shoulder, an angel with the initials "B.M.", is a reminder of her mother.

She has two brothers, Brack and Scott, and her first cousin is tennis player, Taylor Dent.

In January 2004, she began dating Florida Marlins baseball player Matt Treanor and the two were engaged in March 2004. They wed in November 2004.

May-Treanor is listed as currently residing in Coral Springs, Florida though she and her husband also own a home in Long Beach, California.

She is a fan of, and friends with, basketball star Jason Kidd. The tattoo of a roman numeral five on her lower back is a tribute to Kidd, who wore #5 on his jersey for most of his career.