- He was expelled from his high school in Toronto after pretending to be from the school board and convincing a local construction company to start construction of an addition onto the high school.
- Suffers from obsessive-compulsive disorder and mysophobia (fear of germs). As a result, he will not shake hands with people.
- Has a bikini wax named after him, for his clean-shaven head.
- He was awarded a star on Canada's Walk of Fame in Toronto on September 19, 2009. He is the third game show host to be inducted (the first was Monty Hall in 2002 and the second was Alex Trebek in 2006).
- Mandel suffers from attentive deficit hyperactivity disorder (ADHD).
- Instead of shaking hands, a tap fist became a sort of his signature.
- Once an opening act for Diana Ross in Las Vegas, Nevada.
- His acting mentor was William Daniels, whom he credits as his favorite mentor/best friend.
- Best known by the public for his role as Dr. Wayne Fiscus on St. Elsewhere (1982).
- He was awarded a Star on the Hollywood Walk of Fame for Television at 6366 Hollywood Boulevard in Hollywood, California on September 4, 2008.
- His idol was Julie London.
- His daughter, Jackelyn Shultz, is a teacher.
- An alumnus of Beth David B'nai Israel Beth Am's Hebrew School where he celebrated his bar mitzvah.
- Revealed that he had a wonderful chemistry with William Daniels on St. Elsewhere (1982).
- Along with William Daniels, Ed Begley Jr., Stephen Furst and David Morse, Mandel attended the 100th Birthday of his acting mentor Norman Lloyd on 9 November 2014.
- Four of his close friends and fellow comedians Norm MacDonald, Bob Saget, Louie Anderson and Gilbert Gottfried all passed away in a 7-month window from September 2021 to April 2022 (all of them in their 60s). Mandel stated this was one of the biggest 'blows' he has had in losing friends/fellow comedians.
- Friends with Jay Leno.
- First shaved his head during a particularly bad bout of his mysophobia. Has been clean shaven ever since.
- Hospitalized for irregular heartbeat in Toronto, Canada. (January 2009)
- Has color blindness and has contacted COVID-19 at the 2022 Kids' Choice Awards, which led him to physical and mental health struggles, including drug and substance abuse.
- His road manager is Rich Thurber.
- Was once food poisoned by eating contaminated chicken.
- Has two grandchildren: Abby and Axel.
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