Born in New York City and educated at Queensborough Community College, she appeared on Broadway starring in Chicago, Bob Fosse’s Dancin and Dreamgirls. Also she was a choreographer for Whitney Houston’s world tour from 1988–1992. She also appeared as a dancer in Natalie Cole's video for "Pink Cadillac" in 1988.

Since the early '90s, Alexander has concentrated on film and TV, playing the character Catherine Duke on NewsRadio and the recurring character Jackie Robbins on ER. She is well known for her starring role as a mother addicted to drugs named Fran in The Corner. She has made guest appearances on Law & Order: Special Victims Unit, NYPD Blue, La Femme Nikita. She used to portray the character Alexx Woods, a medical examiner in the forensics-related drama CSI: Miami.

Khandi starred in the movie CB4 with Chris Rock and Charlie Murphy. Other film credits include Dark Blue, Sugar Hill, Menace II Society, House Party 3, There's Something About Mary, Rain, and Poetic Justice.

Khandi finished the 2007-2008 season of CBS Hit Show CSI: Miami, but is not returning the following season. Her final appearance aired Monday, May 5, 2008.