Melatonin is a molecule synthesized by the pineal gland, as well as by other organs, such as the retina, bone marrow, immune cells, and mucosa of the gastrointestinal tract, including the salivary glands. Melatonin exerts numerous physiological functions in the body, acting on the membrane and nuclear receptors of the cells. Due to its amphiphilic properties, it is able to enter all cells and cellular compartments. Melatonin is found in the oral cavity; in saliva, and in gingival crevicular fluid, where it exerts local effects. Melatonin activates the immune system by stimulating phagocytes; it regulates the inflammatory response by controlling cytokine, leukotriene, and prostaglandin secretion; by neutralizing the free radicals it protects the cells from oxidative damage. Melatonin has a vital role in bone health- it inhibits osteoclast-mediated bone resorption and it stimulates osteoblasts to synthesize new bone, which in turn secrete collagen and other proteins of the bone matrix. Beneficial effects of melatonin in the diseases of the oral cavity have been reported; it diminishes inflammation and bone resorption in periodontal disease, accelerates dental implant osseointegration and post-extraction wound healing, it possesses oncostatic properties – antiproliferative, antiangiogenic, proapoptotic and immunostimulating; it reduces the severity of chemo- and radiotherapy-induced oral mucositis and it has antimicrobial effect against the viral and fungal infections of the oral cavity.