Melatonin, a hormone produced by the pineal gland, is known for regulating circadian rhythms and has emerging therapeutic potential in psychiatric disorders. This systematic review examines evidence from clinical and preclinical studies to assess melatonin's efficacy in the following conditions: depression, anxiety, bipolar disorder, and schizophrenia. Beyond its role in circadian regulation, melatonin exhibits antioxidative, anti-inflammatory, and immunomodulatory properties, which intersect with nutrition, lifestyle medicine, and psychoneuroimmunology (PNI). The review finds that melatonin improves sleep quality, restores circadian balance, and modulates stress-related neuroimmune pathways. It also supports neuroplasticity and reduces oxidative stress, contributing to resilience against psychosocial and environmental stressors. Lifestyle factors, including diet, exercise, and sleep hygiene, enhance melatonin's effects, positioning it as a valuable component of multimodal treatment strategies. Within the PNI framework, melatonin facilitates communication between the nervous and immune systems, offering potential for targeted psychiatric interventions. This synthesis underscores melatonin's promise as a therapeutic and adjunctive strategy in personalized mental health care. Future research should prioritize rigorous clinical trials, biomarker-driven patient stratification, and integrative approaches combining melatonin with lifestyle interventions and digital health tools to optimize its therapeutic impact.
