Gastrointestinal symptoms are prevalent in patients with systemic mastocytosis and contribute to morbidity. In indolent disease, the symptoms, which include heartburn, abdominal pain, and diarrhea, are largely due to release of mast cell mediators but may be due to other factors. A thorough evaluation that incorporates abdominal imaging and endoscopy with intestinal biopsy assists with diagnosis and management. Patients with advanced mastocytosis experience signs and symptoms of gastrointestinal dysfunction owing to the massive infiltration of clonal mast cells in the tissues. The gastrointestinal symptoms in systemic mastocytosis are treatable with a combination of therapies, including those directed at mast cells.