Teriflunomide is an oral monotherapy used to treat relapsing multiple sclerosis. Although teriflunomide may be associated with gastrointestinal symptoms, these events are mild and self-limiting. We present a 39-year-old female who developed severe diarrhea and lost 20 pounds within 3 weeks of starting teriflunomide. Despite discontinuing teriflunomide and undergoing cholestyramine washout, her symptoms persisted. Celiac disease on genetic testing was positive, but no anti-transglutaminase and anti-endomysial antibodies were detected. She underwent colonoscopy and biopsy was consistent with lymphocytic colitis. Remission was achieved within days of starting budenoside. Our case describes a rare, but serious, gastrointestinal adverse event of teriflunomide.