Margolyes did not act regularly in film until the mid-1970s, and for a time most of her roles were in little-seen British films including "The Battle of Billy's Pond" (1976), "On a Paving Stone Mounted" (1978) and the experimental "Crystal Gazing" (1982), or small parts in the US-made "Yentl" (1983) and "Little Shop of Horrors" (1986). She gained critical and public attention with her performance as flirtatious spinster Flora Finching in the two-part film adaptation of Charles Dickens' "Little Dorrit" (1988). She followed with an amusing turn as Kevin Kline's outraged mother in the black comedy "I Love You to Death" (1990), a highly successful one-woman touring show, "Woomen, Lovely Woomen" (1991), spotlighting Dickensian females, and a failed sitcom, "Frannie's Turn" (1992). Margolyes received her greatest popular acclaim (under heavy padding) as the elderly, sharp-tongued Mrs. Mingott, the primary source of comic relief in "The Age of Innocence" (1993).
The widely expected Oscar nomination for Margolyes' work as Mrs. Mingott surprisingly did not appear, but the actress continued in prominent roles in ambitious films like "Immortal Beloved" (1994). She also extended her stream of oddball efforts with "Ed and His Dead Mother" (1993), as the deceased titular parent, wielding a chainsaw and eating bugs with her customary glee. Voiceover work kept her busy as well, her most popular effort in this vein being Fly, the maternal but pragmatic dog who learns about not compromising one's dreams from a pig named "Babe" (1995). She returned for the sequel, "Babe: Pig in the City" (1998) and also lent her voice tp the Matchmaker of "Mulan" (1998). Margolyes continued to work frequently, appearing in mainstream films such as "Magnolia" (1999) and "End of Days" (1999), but it was in 2002 that she nabbed the role that would make her a star, at least among juvenile moviegoers: Professor Sprout, the delightful proponent of mandrake in "Harry Potter and the Chamber of Secrets." The actress continued to work in a variety of projects, most notably playing one of the circle surrounding the aging theater diva (Annette Bening) in "Being Julia" (2004) and actor Peter Sellers' frighteningly ambitious mother in the HBO biopic "The Life and Death of Peter Sellers" (2004).