Matlin received an honorary Doctorate of Humane Letters degree from Gallaudet University in 1987. In October 2007, she was appointed to the Gallaudet University Board of Trustees. In 1988, Matlin received the Samuel S. Beard Award for Greatest Public Service by an Individual 35 Years or Under, an award given out annually by Jefferson Awards.

In 1989, Matlin portrayed a deaf widow in the television movie Bridge to Silence. In that role, she spoke in addition to using sign language. People magazine did not like the film, but praised Matlin’s work, writing, “the beautiful, emotionally moving Matlin is too good for this well-intentioned but sentimental slop.” She was nominated for a Golden Globe for her work as the lead female role in the television series Reasonable Doubts (1991–1993). Matlin was nominated for an Emmy Award for a guest appearance in Picket Fences (1992) and became a regular on that series during its final season (1996). She played Carrie Buck in the 1994 television drama Against Her Will: The Carrie Buck Story, based on the 1927 United States Supreme Court case Buck v. Bell 274 U.S. 200. In that role, Matlin portrayed a hearing woman for the first time in her career, which earned her a CableACE nomination for Best Actress. She had a prominent supporting role in the drama It’s My Party (1996).

In 1991, Matlin received the Bernard Bragg* Young Artists Achievement Award at the Annual International Creative Arts Festival sponsored by the Center on Deafness in Chicago.

Matlin married Burbank police officer Kevin Grandalski on August 29, 1993, at the home of actor Henry Winkler, five days after her 28th birthday. They first met while she was filming a scene from Reasonable Doubts outside the studio grounds; the police department had assigned Grandalski to provide security and control traffic. They have four children: Sarah (born 1996), Brandon (born 2000), Tyler (born 2002), and Isabelle (born 2003).

Matlin is actively involved with a number of charitable organizations, including Easter Seals (where she was appointed an Honorary board member), the Children Affected by AIDS Foundation, Elizabeth Glaser Pediatric AIDS Foundation, VSA arts, and the Red Cross Celebrity Cabinet. She was appointed by President Clinton in 1994 to the Corporation for National Service and served as chair of National Volunteer Week. Matlin was a participant in the first-ever national television advertising campaign supporting donations to Jewish federations. The program featured “film and television personalities celebrating their Jewish heritage and promoting charitable giving to the Jewish community” and included Greg Grunberg, Joshua Malina, Kevin Weisman, and Jonathan Silverman.

In 2002, Matlin published her first novel, titled Deaf Child Crossing, which was loosely based on her own childhood. She later wrote and published a sequel titled Nobody’s Perfect, produced on stage at the John F. Kennedy Center for Performing Arts in partnership with VSA Arts in October 2007. In 2004, she starred in the movie What the Bleep Do We Know!? as Amanda. Also in 2003, she hosted the 3rd Annual Festival for Cinema of the Deaf in Chicago.

In 2006, she played a deaf parent in Desperate Housewives. She had a recurring role in My Name Is Earl as public defender for Joy Turner (who made many jokes about Matlin’s deafness at Matlin’s expense), and played the mother of one of the victims in an episode of CSI: NY. That same year, Matlin was cast in season 4 of The L Word as Jodi Lerner, a lesbian sculptor. She appeared in season 4 (2007), season 5 (2008), and season 6 (2009) as the girlfriend of one of the show’s protagonists, Bette Porter, played by Jennifer Beals.

On February 4, 2007, and February 7, 2016, Matlin interpreted the “Star Spangled Banner” in American Sign Language at Super Bowl XLI in Miami, Florida, and at Super Bowl 50 in Santa Clara, California, respectively. In January 2008, she appeared on Nip/Tuck as a television executive.

In 2008, Matlin participated as a competitor in the sixth season of ABC’s Dancing with the Stars. Her dance partner was newcomer Fabian Sanchez. Matlin and Sanchez were the sixth couple eliminated from the competition.

On May 6, 2009, Matlin received a star on the Hollywood Walk of Fame.

On November 8, 2009, Matlin appeared on Seth & Alex’s Almost Live Comedy Show, hosted by Seth MacFarlane and Alex Borstein. After Borstein imitated Matlin calling MovieFone and singing “Poker Face,” Matlin herself appeared and launched into a comical tirade against Borstein over being made fun of, and how she was not invited to provide her own voice for Family Guy. Matlin went on to voice Stella, Peter Griffin’s coworker, in the Season 10 episode “The Blind Side;” Stella later became a recurring character.

On April 14, 2009, Matlin released an autobiography, I’ll Scream Later. In it, she describes her drug abuse and how it drove her to check herself into the Betty Ford Center. She also tells about her rocky, two-year relationship with her significantly older Children of a Lesser God co-star William Hurt, who she claims was physically abusive to her. She also addresses the sexual abuse she suffered as a child at the hands of her female babysitter.

In 2010, Matlin produced a pilot for a reality show she titled My Deaf Family, which she presented to various national network executives. Although they expressed interest, no network purchased rights to the show. On March 29, 2010, Matlin uploaded the pilot to YouTube and launched a viral marketing campaign.

On July 26, 2010, Matlin signed a speech at an event commemorating the 20th anniversary of the Americans with Disabilities Act.

In the following year, Matlin was a finalist on the NBC show The Celebrity Apprentice, competing to win money for her charity, The Starkey Hearing Foundation, finishing in second place. However, on one episode of The Celebrity Apprentice, “The Art of the Deal”, which was transmitted on April 3, 2011, she raised more funds than had ever been raised for charity in a single event on any television show before, $986,000. Donald Trump, who was then hosting The Celebrity Apprentice, then donated an additional $14,000 to make the contribution an even million.

In 2013, Matlin played herself in No Ordinary Hero: The SuperDeafy Movie. As of January 2015, Matlin also acted as the ACLU’s celebrity ambassador for disability rights.

In recognition of her philanthropic work and her advocacy for the inclusion of people with disabilities, Matlin received the 2016 Morton E. Ruderman Award in Inclusion, a $120,000 prize given annually by the Jay Ruderman of the Ruderman Family Foundation to one individual whose work excels at promoting disability inclusion. She won the Henry Viscardi Achievement Awards for disability advocacy in 2014. She was awarded an Academy Award for Best Actress for Children of a Lesser God and to date is the only deaf performer to have won an Academy Award.

Matlin played the recurring character of Melody Bledsoe on Switched at Birth. In September 2015, she made her Broadway debut in the revival production of the musical Spring Awakening.

Beginning in 2017, Matlin played the recurring role of Harriet on the Syfy television series, The Magicians.

On July 31, 2017, it was announced by Deadline that Matlin joined as a series regular in the third season of the ABC thriller Quantico. She starred in the role of ex-FBI agent Jocelyn Turner.

In 2019, Marlee Matlin was mentioned in an article by Hearing Like Me as somebody that could bring more #DeafTalent to “Life and Deaf,” a new comedy show that aims to explore the life of a kid with deaf parents. The new series, which was set in the 1970’s, will star the award-winning actress and deaf activist Marlee Matlin. This show was to be executive produced by Marlee Matlin according to Deadline.