This review discusses the presence of melatonin in extrapineal tissues and organs in mammals, including humans. Melatonin is synthesized from tryptophan via serotonin and is present in various tissues such as 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. Melatonin is found in most biological fluids, including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk, with concentrations in some fluids exceeding those in blood. Melatonin's physiological regulation of cell homeostasis and potential therapeutic applications are important due to its continual availability at the cellular level. The review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids, highlighting its antioxidant, anti-inflammatory, and genomic effects. Melatonin receptors, including MT1 and MT2, mediate its effects, while other receptors such as ROR orphan receptors are involved in nuclear actions. Melatonin synthesis pathways involve AANAT and ASMT enzymes, and its production is regulated by various factors, including photoperiod and other signaling pathways. Melatonin's actions include protecting cells from oxidative and inflammatory damage, modulating antioxidant gene transcription, and influencing circadian rhythms. Melatonin also has dual effects, acting as both an antioxidant and pro-oxidant under certain conditions. Its presence in the brain, retina, lens, cochlea, immune system, skin, and gastrointestinal tract is well documented, with various functions in these tissues. Melatonin's role in protecting against oxidative stress, modulating circadian rhythms, and its potential therapeutic applications are discussed. The review also highlights the importance of melatonin in various physiological processes, including neuroprotection, immune function, and skin protection. Overall, melatonin's presence in extrapineal tissues and its diverse functions make it a key molecule in maintaining physiological homeostasis and protecting against various diseases.This review discusses the presence of melatonin in extrapineal tissues and organs in mammals, including humans. Melatonin is synthesized from tryptophan via serotonin and is present in various tissues such as 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. Melatonin is found in most biological fluids, including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk, with concentrations in some fluids exceeding those in blood. Melatonin's physiological regulation of cell homeostasis and potential therapeutic applications are important due to its continual availability at the cellular level. The review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids, highlighting its antioxidant, anti-inflammatory, and genomic effects. Melatonin receptors, including MT1 and MT2, mediate its effects, while other receptors such as ROR orphan receptors are involved in nuclear actions. Melatonin synthesis pathways involve AANAT and ASMT enzymes, and its production is regulated by various factors, including photoperiod and other signaling pathways. Melatonin's actions include protecting cells from oxidative and inflammatory damage, modulating antioxidant gene transcription, and influencing circadian rhythms. Melatonin also has dual effects, acting as both an antioxidant and pro-oxidant under certain conditions. Its presence in the brain, retina, lens, cochlea, immune system, skin, and gastrointestinal tract is well documented, with various functions in these tissues. Melatonin's role in protecting against oxidative stress, modulating circadian rhythms, and its potential therapeutic applications are discussed. The review also highlights the importance of melatonin in various physiological processes, including neuroprotection, immune function, and skin protection. Overall, melatonin's presence in extrapineal tissues and its diverse functions make it a key molecule in maintaining physiological homeostasis and protecting against various diseases.