Cancer is a pervasive health challenge, affecting millions of lives worldwide each year. In 2020 alone, nearly 19.3 million new cases were diagnosed globally. Oral mucositis (OM), a distressing side effect of cancer chemotherapy, manifests as painful ulcers in the oral mucosa, hampering basic functions like eating and speaking. The current therapeutic options for managing mucositis pain, including oral health care, anti-inflammatory agents, local anaesthetics, oral decontamination, benzydamine hydrochloride rinse, and low-level laser therapy are associated with significant side effects and high costs. So, natural products containing bioactive compounds have emerged as promising candidates for managing oral mucositis. This chapter explores the potential of diverse natural sources, including Aloe vera, Calendula officinalis, honeybee etc. in preventing and treating OM. These natural products possess biological activities, such as antimicrobial, antiviral, anti-inflammatory, analgesic, and wound-healing properties, attributed to their different bioactive compounds. Recent clinical studies examining the effectiveness and safety of these natural remedies are also discussed.