Colonic malakoplakia is a rare chronic granulomatous disease that can involve many organs such as the lung, brain, pancreas, bone, adrenal glands, and genitourinary tract. The most common site of involvement outside the genitourinary tract is the gastrointestinal tract. We report a case of colonic malakoplakia who presented with unintentional weight loss, abdominal pain, and chronic diarrhea. There was a history of lupus nephritis and Sjogren disease, receiving various immunosuppressive drugs. Physical examination other than pallor was unremarkable in this patient, but colonoscopy revealed multiple polyps in the rectum with a cobblestone appearance in the cecum. The histopathological assessment showed infiltration of numerous lymphoplasma cells and neutrophils in the lamina propria, and rare Michaelis-Gutmann bodies were seen in foamy epithelioid histiocytes. These findings are suggestive of malakoplakia. We treated the patient with tetracycline, and after 3 months of follow-up, clinical improvement was achieved.