The former "Little House on the Prairie" star cited irreconcilable differences in her divorce petition, which was filed Monday in Los Angeles.
The filing states the couple separated in January, shortly after their 16th wedding anniversary.
Gilbert served two terms as president of the Screen Actor's Guild, and Boxleitner has appeared in numerous movies and television series, including "Babylon 5" and both "Tron" films.
The couple has a 15-year-old son together.
Gilbert, who played Laura Ingalls on "Little House," is seeking joint custody of their son and no spousal support from Boxleitner.