Introduction: Oral mucositis is considered as the most debilitating and unavoidable side effect of chemoradiother- apy for head and neck cancers. Keratin is one of the protective factors present in the superficial layers of the oral epithelium. Break in the integrity of the epithelial tissue seen in radiation mucositis is suggestive of production of proteolytic enzymes which help to dissolve the keratin in the epithelium. Methods: This randomized controlled trial was conducted among eighty head and neck cancer patients scheduled to undergo radiotherapy. Patients were divid- ed into control group (40 Patients) who received artificial saliva(carboxymethyl cellulose base)and the study group (40 Patients) who received virgin coconut oil in the form of oral rinses 4 times daily during the entire course of the radiotherapy. Salivary proteolytic levels were measured in optical density units, spectrophotometrically using mod- ification of Erlanger et al.’s (1961) method along with clinical grading of the radiation mucositis. Results: The study showed high degree of correlation between salivary proteolytic levels and radiation mucositis. The levels of salivary proteolytic activity and radiation mucositis were lower in the patients who received virgin coconut oil as compared to those who received artificial saliva. Conclusion: The study showed better therapeutic efficacy with virgin coconut oil as compared to artificial saliva in the management of radiation mucositis in head and neck cancer patients.