- Delivered the eulogy at the memorial service for her friend and mentor, Patty Duke, on April 16, 2016. Duke was "Annie Sullivan" to Gilbert's "Helen Keller" in the 1979 production of The Miracle Worker (1979). Similarly, in June 2005, Patty Duke gave the eulogy at Anne Bancroft's memorial service. Bancroft was "Annie Sullivan" to Duke's "Helen Keller" in the original The Miracle Worker (1962) in 1962.
- Michael Landon Jr. took her to her high school senior prom (1981).
- Her acting mentors were the late Michael Landon and the late Patty Duke.
- Was one of 500 young girls who auditioned for the role of Laura Ingalls Wilder in the TV series Little House on the Prairie (1974) and she was the only one whose screen test was sent to be considered by NBC. It was Michael Landon's daughter Leslie Landon who told Melissa that she had won the role of Laura when the two of them stood in line at their school cafeteria.
- She appeared in 191 of the 205 episodes of Little House on the Prairie (1974), more than anyone else.
- Had a combined family with her ex-husband, Bruce Boxleitner: Bruce had two sons, Sam Boxleitner (b. 1980) and Lee Boxleitner (b. 1985). Melissa became a mother when her first child, Dakota Brinkman (Dakota Paul Brinkman), was born on Monday, May 1, 1989, while she was married to Bo Brinkman. She had one son with Bruce, Michael Garrett Boxleitner, who was born on Friday, October 6, 1995.
- Her production company is "Half-Pint Productions".
- On April 24, 2013, she married her longtime boyfriend Timothy Busfield (her third marriage) following a three-month-long engagement.
- As an actress, she was highly influenced by Michael Landon.
- Gave birth to her second child at age 31, son Michael Garrett Boxleitner, on October 6, 1995. Child's father is her second ex-husband, Bruce Boxleitner.
- Adopted half-sister of Sara Gilbert. Sara is the natural daughter of Barbara Cowan and Harold Abeles. Cowan and late husband Paul Gilbert together adopted Melissa and Jonathan Gilbert (they are not biologically related to each other). Sara took her stepfather's surname when she began acting in 1984.
- Had a highly publicized relationship with Rob Lowe during the 1980s, and they were reportedly at one time engaged.
- Has highly praised Michael Landon for her stardom to acting.
- Revealed that she had a wonderful working relationship with Michael Landon on Little House on the Prairie (1974).
- Was introduced to last ex-husband Bruce Boxleitner by his ex-wife, Kathryn Holcomb.
- Her childhood idol was Shirley Temple.
- Melissa was considered for the voice role of Penny in Disney's The Rescuers (1977).
- She was awarded a Star on the Hollywood Walk of Fame for Television at 6249 Hollywood Boulevard in Hollywood, California on March 13, 1985.
- On August 14, 2015, she announced that she is running for a seat in Congress from Michigan.
- In national voting completed on Friday, 2 November 2001, she was elected president of the Screen Actors Guild, taking the position held since November 1999 by William Daniels, who declined to run for another term. She held the position until 2005, when she was replaced by Alan Rosenberg.
- Gave birth to her first child at age 24, son Dakota Brinkman, on May 1, 1989. Child's father is her first ex-husband, Bo Brinkman.
- In her autobiography, she lists Charlie Brill as her godfather and his wife, actress/comedienne Mitzi McCall, as her godmother.
- Both her ex-husbands (Bo Brinkman and Bruce Boxleitner) played Confederate officers in Gods and Generals (2003).
- After Michael Landon was seeing Cindy Clerico, Gilbert did not keep in touch with him after Little House on the Prairie (1974), except for that one time before his death, she saw her TV father on The Tonight Show Starring Johnny Carson (1962), where it was Landon's final TV performance.
- Ranked #31 in VH1's list of the "100 Greatest Kid Stars".
- Inducted (as a cast member of Little House on the Prairie (1974)) into the Hall of Great Western Performers of the National Cowboy & Western Heritage Museum (1998).
- Had not seen not a single episode of Bonanza (1959), that featured her own TV father Michael Landon, until she was cast opposite Landon in Little House on the Prairie (1974).
- Best known by the public for her role as Laura Ingalls Wilder on Little House on the Prairie (1974).
- Aunt of Sara Gilbert's son Levi and daughter Sawyer.
- Goddaughter of Charlie Brill and Mitzi McCall.
- Currently residing in New York City. (May 2022)
- Granddaughter of Harry Crane.
- Close friends with Katie Wagner.
- As of August 2013, was residing in Howell, Michigan.
- Youngest stepsister of Claudia Cowan. Stepdaughter of Warren Cowan.
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