Pomegranate (Punica granatum L.) is a long-lived and drought-tolerant plant. It is rich in bioactive components which has strong antioxidant, anti-inflammatory and anticancerous properties. Methotrexate (MTX) is an antifolate cytotoxic drug used to treat certain types of malignancies and several autoimmune diseases. MTX exerts its cytotoxic effects not only against cancer cells but also upon normal cells. Thus, a wide range of adverse reactions is inevitable; especially gastrointestinal side effects. Aims: This narrative review examines the existing literature in order to find out whether or not pomegranate is suitable to act against MTX induced mucosal damage.