Gastrointestinal (GI) symptoms are commonly reported in patients with mast cell disease. GI involvement in systemic mastocytosis is heterogeneous and symptoms may be caused by infiltration of abnormal mast cells in the GI tract and/or by the downstream effect of mast cell mediators on GI tissues. GI symptoms described the monoclonal mast cell activation syndrome are best characterized in the context of acute anaphylaxis. The presence of GI symptoms and a subjective response of symptoms to anti-mast cell mediator therapy are considered qualifying criteria in the diagnosis of the idiopathic mast cell activation syndrome. Antimediator therapy may help alleviate GI symptoms in mast cell disease.