Oral mucositis is a frequent adverse effect of cancer treatment that includes radiotherapy (RT) and chemotherapy (CT). It is related to worse outcomes because of pain, nutritional problems, effects on quality of life, changes in cancer treatment, the risk of infection, and financial costs. It affects 20% to 80% of people receiving chemotherapy, and almost all patients receive head and neck radiation therapy. This review presents the current understanding and discusses evidence-based clinical management strategies for oral mucositis. The current model of mucositis pathogenesis is comprised of five broad stages. The two widely used grading systems for routine clinical care and research on mucositis are the WHO (World Health Organization) and Oral Mucositis Scale and the National Cancer Institute's Common Toxicity Criteria (NCI-CTC). The effective use of assessment scales, nonpharmacologic treatment modalities such as good professional oral hygiene, cryotherapy, and photobiomodulation, and pharmacologic therapies such as KGF-1 (palifermin) and benzydamine-containing mouthwash are important for mucositis prevention, and topical morphine is effective for the treatment of mucositis induced by radiotherapy or chemotherapy. Mucoadhesive hydrogel and anti-inflammatory medications such as celecoxib, misoprostol, and rebamipide are reported to be effective for radiation-induced mucositis. However, additional experimental studies are required to confirm the evidence.