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Following her departure from ER Margulies worked on stage and screen. Margulies's in-laws are Jane Lindsay and the academic Kenneth Lieberthal. She starred as the protagonist and narrator (Morgaine) in the 2001 TNT miniseries The Mists of Avalon and participated in the 2002 documentary film Searching for Debra Winger.
After several small television roles Margulies achieved both critical and commercial success in her role as Nurse Carol Hathaway on NBC's long-running medical drama ER for which Julianna Margulies won an Emmy Award. After her departure from ER in 2000 Margulies appeared in the 2001 miniseries The Mists of Avalon and voiced the role of Neera in Disney's CGI film Dinosaur.