Oral mucositis is a major clinical challenge in oncology and is characterized by pain and inflammation of the mucous membrane surface resulting from radiotherapy for head and neck cancer or from chemotherapeutic agents. Manifestations range from a burning sensation to ulcer formation that affect the patients’ quality of life by producing pain and discomfort on swallowing, ultimately leading to malnutrition and dehydration. Due to complications arising from the use of chemical drugs, in recent decades, increasing attention has been paid to natural-based agents. The results from several studies evaluating natural products for the prevention or reduction of chemotherapy- and radiotherapy-induced oral mucositis are promising. This comprehensive review aims to provide updated information concerning the natural agents that are effective against mucositis in cancer patients receiving radiotherapy and/or chemotherapy.