Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland in a circadian fashion. lt is also synthesized in other organs, in which exerts local effects. Melatonin is primarily involved in the regulation of circadian rhythms, but it has a wide functional activities, affecting almost ali tissues and organs. Moreover, multiple molecular targets of melatonin have been identified, and its actions are both receptor-mediated and receptor-independent with potent antioxidant activity. Nowadays it is mainly used as a dietary supplement for sleep regulation and re-synchronization of disrupted circadian rhythms. Melatonin has very low toxicity, but its limited oral bioavailability and short half-life are affecting its tissue availability negatively. Since melatonin receptors display a very wide distribution in the body, putative therapeutic indications of this compound are multiple. This article is focused on the potential therapeutic implications of melatonin in the oral cavity. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and protects against inflammatory processes and cellular damage caused by the reactive oxygen species. As a result of these actions, melatonin may be used therapeutically in the oral cavity to treat gingivitis and periodontitis, prevent caries, reduce potential toxic effects of materials used in dentistry, accelerate healing of postsurgical wounds caused by tooth extractions and other oral surgeries, promote osseointegration of dental implants and may also impede the progression of oral cancer. Specific studies aimed to develop new and more efficient topical delivery systems are necessary to extend the therapeutic possibilities of melatonin to treat oral diseases.