Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that affects many organ systems with varying disease severity. GPA commonly affects the sinuses and lung parenchyma. However, GPA can affect the gastrointestinal tract and may present as colitis. Immunosuppressive therapy, like rituximab (RTX), is used for the management of this disease. Rituximab is generally well-tolerated but has rare side effects that have been shown to mimic colitis in inflammatory diseases. Our case is a 44-year-old female with a history of GPA who presented with dysphagia, abdominal pain, and diarrhea. The patient received a maintenance dose of RTX six months before the presentation. The patient was seronegative for anti-neutrophilic cytoplasmic antibodies against proteinase 3 (PR3 ANCA). Infectious etiology was ruled out. Esophagogastroduodenoscopy (EGD) and colonoscopy showed esophageal bleeding ulcers and diffuse colonic inflammation, respectively. Pathology was consistent with esophagitis and colitis. Colonic mucosal biopsy failed to show evidence of vasculitis. The patient was treated with sucralfate and intravenous pantoprazole with an improvement in the symptoms. The repeat endoscopy on an outpatient basis showed the patient had full mucosal healing, including histological healing. Our patient likely had rituximab-induced colitis and esophagitis.