Intestinal mucositis (IM) is a common side effect of several anticancer medications, including 5-fluorouracil (5-FU), and can lead to treatment disruptions and compromised outcomes. IM has severe clinical effects such as diarrhea, erythematous mucosal lesions, and the development of ulcers accompanied by excruciating pain. This study aimed to evaluate the mucoprotective effects of ellagic acid on 5-FU-induced IM in mice. Mice were administered normal saline intraperitoneally for six days, followed by intraperitoneal injection of 5-FU for four days at a dose of 50 mg per kilogram. Ellagic acid was orally administered to the mice in groups III and IV in two doses (5 mg and 10 mg), with a one-hour time separation from 5-FU for ten days. At the end of the experiment, small intestine tissue was collected to measure the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and inflammatory cytokines (IL-6, IL-B, TNF) using ELISA assay. Pre-treatment with ellagic acid led to a significant decrease in pro-inflammatory cytokines and improved antioxidant enzyme levels compared to the 5-FU group. Histopathological analysis demonstrated the mucoprotective effect of ellagic acid against 5-FU-induced intestinal changes, including villi atrophy, damage to stem cells, infiltration of inflammatory cells in the mucosal layer, edema, damage to muscular mucosa, and decreased oxidative stress production, such as MDA. These results suggest that ellagic acid may be a potential candidate for treating IM induced by antineoplastic drugs.