Smith was married to actor Christopher Grove from 1990 to 1992 and Daniel Erickson from 2002 to 2008. She enjoys writing and painting. During the first season of Herman's Head, Smith taught herself to paint by copying other artists. She released a children's book titled I, Lorelei in 2009 and her story "The Race" was included in the book Just Humor Me.
Smith was born, in Paris. Her father, Joseph Smith, worked for United Press International in Paris and moved to Washington, D.C., in 1966, where he became The Washington Post's first official obituary editor. Her mother, Martha Mayor, was a paper conservator for the Freer and Sackler Galleries at the Smithsonian Institution. Smith's parents later divorced. Smith labeled her family "upper crust and reserved". As a child, Smith was often teased because of her unusual voice. Smith has stated: "I've sounded pretty much the same way since I was six. Maybe [my voice is] a little deeper now." She made her acting debut in a sixth-grade play.