This review discusses the extrapineal sources, regulation, and potential functions of melatonin, an indoleamine synthesized from tryptophan. Melatonin is produced not only by the pineal gland but also in various extrapineal tissues and organs, including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. The presence of melatonin-synthesizing enzymes and receptors in these tissues suggests that melatonin has multiple roles beyond its well-known circadian regulatory functions. Melatonin's antioxidant and anti-inflammatory properties, as well as its effects on mitochondrial homeostasis, are highlighted. The review also explores the dual nature of melatonin's actions, where low concentrations act as antioxidants, while high concentrations can exhibit pro-oxidant effects in certain conditions. The regulation of melatonin synthesis in different tissues is discussed, emphasizing the importance of post-transcriptional regulation and the role of specific signaling pathways. Additionally, the review examines the specific functions of melatonin in the brain, retina, lens, cochlea, immune system, skin, and gastrointestinal tract, highlighting its potential therapeutic applications in various diseases.This review discusses the extrapineal sources, regulation, and potential functions of melatonin, an indoleamine synthesized from tryptophan. Melatonin is produced not only by the pineal gland but also in various extrapineal tissues and organs, including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. The presence of melatonin-synthesizing enzymes and receptors in these tissues suggests that melatonin has multiple roles beyond its well-known circadian regulatory functions. Melatonin's antioxidant and anti-inflammatory properties, as well as its effects on mitochondrial homeostasis, are highlighted. The review also explores the dual nature of melatonin's actions, where low concentrations act as antioxidants, while high concentrations can exhibit pro-oxidant effects in certain conditions. The regulation of melatonin synthesis in different tissues is discussed, emphasizing the importance of post-transcriptional regulation and the role of specific signaling pathways. Additionally, the review examines the specific functions of melatonin in the brain, retina, lens, cochlea, immune system, skin, and gastrointestinal tract, highlighting its potential therapeutic applications in various diseases.