Autoimmune enteropathy (AIE) is a rare disease that has been observed in both children and adults. It typically manifests with symptoms of diarrhea, requiring long-term immunosuppression. Endoscopically, the duodenum typically exhibits villous blunting with partial or complete villous blunting, deep crypt lymphocytosis, increased apoptotic bodies, and minimal intraepithelial lymphocytosis on histologic analysis. The pathophysiology of AIE likely involves a hyperactive immune state in the setting of a T-cell regulatory defect, resulting in destruction of the enterocyte. We report a case of a 49-year-old woman who presented with refractory diarrhea, diagnosed as AIE. After failing multiple conventional therapies, she demonstrated clinical and histologic response to abatacept, a selective modulator of T-cell activation. We aim to increase awareness of this rare inflammatory disorder and new treatment options for this debilitating condition.