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Premature ovarian failure (POF) is characterized by impairment of ovarian function unrelated to elevatedfollicle-stimulating hormone (FSH) before the age of 40. The consequence of POF is severe and distinctive, presentingfrom infertility to symptoms caused by hormone deprivation. The mechanism of POF remains unclearand current treatments are therefore ineffective. Melatonin (N-acetyl-5-methoxytryptamine) is a neuroendocrinalhormone chiefly secreted by the pineal body. Melatonin exerts extensive physiological and pharmacologicaleffects on the biological rhythm, oxidative stress, reproduction, autoimmune and tumourigenesis. However,current researches have not yet brought melatonin into the study of POF. In the present review, we have involvedstate-of-the-art research progress of melatonin in ovary with regard to oxidation, follicle formation and function,and ovarian autoimmune disorders since these aspects mainly dispose to POF development. The features thatmelatonin scavenges reactive oxygen species (ROS), directly and indirectly induces follicle maturation, ovulationand inhibits apoptosis, and modulates autoimmune derangements in the ovaries are highly indicative that melatonincan effect in combating POF. Also, in this respect we have discussed the possibility of applying melatoninin the treatment of POF and have listed evidence of studies in vitro and in vivo. Vacant research directions aresubsequently suggested and the future application of melatonin in POF treatment is prospected.