Melatonin is a neurohormone synthesized from the aromatic amino acid tryptophan mainly by the pineal gland of mammals. Melatonin acts as a broad-spectrum antioxidant, powerful free radical scavenger, anti-inflammatory agent, anticarcinogenic factor, sleep inducer and regulator of the circadian rhythm, and potential immunoregulator. Melatonin and reproductive system are interrelated under both physiological and pathological conditions. Oxidative stress, inflammation, and immune dysregulation are associated with the pathogenesis of the female reproductive system which causes endometriosis (EMS), recurrent spontaneous abortion (RSA), and polycystic ovary syndrome (PCOS). Accumulating studies have indicated that melatonin plays pleiotropic and essential roles in these obstetrical and gynecological disorders and would be a candidate therapeutic drug to regulate inflammation and immune function and protect special cells or organs. Here, we systematically review the pleiotropic roles of melatonin in EMS, RSA, and PCOS to explore its pathological implications and treatment potential.