Oral mucositis is a consequence of the toxic effects of chemotherapeutic agents and irradiation on oral mucosa cells. It is estimated that oral mucositis is a complication in 40% of patients receiving chemotherapy, more than 90% of those irradiated for head and neck cancer. This condition is frequently associated with severe pain and inflammation and can cause malnutrition, systemic infections, and low quality of life, as well as limiting chemotherapy doses. The pineal hormone melatonin inhibits the production of free radicals that mediate the toxicity of chemotherapy. The main objectives of this study is to develop and evaluate a novel occlusive bioadhesive system for prophylaxis and/or treatment of oral mucositis based on chitosan and melatonin in order to exploit natural biomaterials as functional biocompatible gels and evaluate the performance of the alternative drug delivery system towards in-vitro generated free-radical mediated inflammation response as a model system for oral mucosatis.