She is currently serving as the national president of the Screen Actors Guild – American Federation of Television and Radio Artists (SAG-AFTRA).

She played Fran Fine in the television sitcom The Nanny (1993–1999), which she created and produced with her then-husband Peter Marc Jacobson.

In the 1980s, she worked as a comedic actress in the films Gorp (1980), The Hollywood Knights (1980), Doctor Detroit (1983), This Is Spinal Tap (1984), and UHF (1989), and made guest appearances on several television series.

The national members of trade union SAG-AFTRA, representing actors and other media professionals, elected Drescher as president, and she took office on October 15, 2021.

Her maternal great-grandmother Yetta was born in Focșani, Romania, and emigrated to the United States,[8] while her father's family came from Poland.

[16] Drescher and Jacobson attended Queens College, City University of New York, but dropped out in their first year because "all the acting classes were filled."

[17] Drescher's first break was a small role as dancer Connie in the movie Saturday Night Fever (1977), in which she delivered the line "So, are you as good in bed as you are on the dance floor?"

During the 1980s, Drescher found success as a character actress with roles in films such as Gorp (1980), The Hollywood Knights (1980), Doctor Detroit (1983), The Big Picture (1989), UHF (1989), Cadillac Man (1990), and memorably in This Is Spinal Tap (1984) as publicist Bobbi Flekman.

In 1990, Drescher appeared on ALF as Roxanne, the wife of grown-up Brian, who had no clue she was a mob boss, in the episode "Future's So Bright I Gotta Wear Shades".

Drescher appeared in Jack (1996), directed by Francis Ford Coppola, The Beautician and the Beast (1997) (for which she was also executive producer) and Picking Up the Pieces (2000) co-starring Woody Allen.

A series about two old high school friends coping with midlife crises, Drescher described the premature plot of the show as "kind of Sex and the City but we ain't getting any!

While the program debuted to strong ratings, it ended its three-week test run to moderate success, resulting in its shelving.

[20][21] The following year, the sitcom Happily Divorced, created by Drescher and her ex-husband, Peter Marc Jacobson, was picked up by TV Land for a ten-episode order.

To promote Happily Divorced, Drescher performed the weddings of three gay couples in New York City using the minister's license she received from the Universal Life Church.

She reprised the role during the North American tour's engagement in Los Angeles, lasting from March through April 2015.

[25] Drescher's previous stage performances include an off-Broadway production of Nora Ephron's Love, Loss, and What I Wore, and Camelot at the Lincoln Center with the New York Philharmonic.

"[27] In 2021, Drescher began her campaign to become president of the Screen Actors Guild - American Federation of Television and Radio Artists (SAG-AFTRA) union, citing both her entertainment and political background (see below).

[5] The strike ended with a tentative deal between the union and the Alliance of Motion Picture and Television Producers which was approved by the SAG-AFTRA board.

[41][42][43] Ayyadurai later said it was not "a formal wedding or marriage," but a celebration of their "friendship in a spiritual ceremony with close friends and her family.

Drescher says: We need to take control of our bodies, become greater partners with our physicians and galvanize as one to let our legislators know that the collective female vote is louder and more powerful than that of the richest corporate lobbyists.

[48]She says her goal is to live in a time when women's mortality rates drop as their healthcare improves and early cancer detection increases.

In September 2008, Drescher, a Democrat, was appointed as a U.S. diplomat by George W. Bush administration's Assistant Secretary of State Goli Ameri.

Her first trip was in late September and included stops in Serbia, Hungary, as well as her ancestral Romania and Poland.

[53] In 2018, Drescher attended a fundraiser gala for Friends of the Israeli Defense Forces (FIDF), which raised $60 million.

[56] Drescher became an ordained minister with the Universal Life Church Monastery so that she could legally officiate LGBT wedding ceremonies.