Oral radiation mucositis is one of the debilitating and dose-limiting acute toxicity during (chemo) radiation or for HNC having a major impact on the patient daily functioning, well-being and quality of life. The unplanned interruption of treatment secondary to mucositis may compromise the treatment and the outcomes if not adequately addressed. Recently, the integrated pathophysiological mechanism of radiation injury has been proposed, aiding development of certain targeted therapies for the prevention and treatment of oral mucositis. Although there are currently no approved agents or strategies that can reliably prevent or treat oral mucositis, there are several agents are under investigation and development. This is an exciting juncture in the development of drugs and drug delivery agents for radiation oral mucositis. This review is to have a peep into currently available options at present to optimally know when these agents can be used and what should be the direction of future research to maximize the therapeutic benefit.