We experienced a case of treatment-resistant eosinophilic gastrointestinal disease (EGID). The patient, a 46-year-old man, presented with a fever, persistent abdominal pain, and an elevated peripheral eosinophil count. Eosinophil infiltration of the intestinal mucosa was also observed, and EGID was diagnosed. Corticosteroid therapy was initiated, but no improvement was seen. However, after mepolizumab (anti-interleukin 5 antibody) was administered, the patient's disease was controlled. Currently, the indications for mepolizumab are limited to bronchial asthma and paraneoplastic eosinophilic polyangiitis, but the experience herein reported suggests its usefulness in the treatment of EGID.