Scardino was born in New York City, to jazz musician parents. His first Broadway credit was as an understudy in The Playroom in 1965. Additional Broadway acting credits include Johnny No-Trump, Godspell, and King of Hearts. Off-Broadway he appeared in The Rimers of Eldritch, The Comedy of Errors, Moonchildren, and I'm Getting My Act Together and Taking It on the Road, he was also the lead in a B horror movie titled Squirm in 1976. He additionally starred in several episodes of the CBS Radio Mystery Theater, which ran from 1974 to 1982. In addition, he served as artistic Director at Playwrights Horizons from 1991 to 1996. On television he appeared on the daytime soap operas The Guiding Light, All My Children, Love Is a Many Splendored Thing, and Another World and the primetime series The Ghost & Mrs. Muir and The Name of the Game. Feature film credits include The People Next Door, Rip-off, Homer, Squirm, Cruising and He Knows You're Alone.

Following his acting on the network soap operas, Scardino began to direct them. He directed episodes of Another World, One Life to Live, and All My Children. He went on to direct plays on and off-Broadway, including the world premiere of Aaron Sorkin's A Few Good Men. He has directed extensively in television, most notably Tracey Takes On... and 30 Rock. Feature film directing work includes Me and Veronica (Venice Film Festival), and Advice from a Caterpillar, winner, best comedy, at Aspen Comedy Festival. He directed the 2013 film The Incredible Burt Wonderstone, starring Jim Carrey and Steve Carell.