Melatonin, a tryptophan-derived hormone, plays a crucial role in mitochondrial quality control (MQC), which involves mitochondrial biogenesis, dynamics, and autophagy. This review summarizes the mechanisms by which melatonin influences mitochondrial function, including its role in mitochondrial biogenesis, dynamics, and autophagy. Melatonin regulates mitochondrial metabolism by modulating acetyl-CoA levels, electron transport chain activity, and oxidative phosphorylation. It also influences the redox state by acting as a potent antioxidant, scavenging reactive oxygen species (ROS) and enhancing antioxidant enzyme activity. Melatonin promotes mitochondrial fusion by upregulating genes such as mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy1 (Opa1), while inhibiting mitochondrial fission by regulating genes like dynamin-related protein 1 (Drp1) and Fission 1 (Fis1). Additionally, melatonin modulates autophagy, either enhancing or suppressing it depending on the cellular context, to maintain mitochondrial homeostasis and prevent oxidative damage. Melatonin is synthesized in various tissues, including the pineal gland, and can be transported into mitochondria. Its regulatory effects on mitochondrial function are essential for maintaining cellular energy supply and preventing mitochondrial-related diseases. The review highlights the potential of melatonin as a therapeutic agent for mitochondrial-related disorders, emphasizing the need for further research to fully understand its mechanisms and applications.Melatonin, a tryptophan-derived hormone, plays a crucial role in mitochondrial quality control (MQC), which involves mitochondrial biogenesis, dynamics, and autophagy. This review summarizes the mechanisms by which melatonin influences mitochondrial function, including its role in mitochondrial biogenesis, dynamics, and autophagy. Melatonin regulates mitochondrial metabolism by modulating acetyl-CoA levels, electron transport chain activity, and oxidative phosphorylation. It also influences the redox state by acting as a potent antioxidant, scavenging reactive oxygen species (ROS) and enhancing antioxidant enzyme activity. Melatonin promotes mitochondrial fusion by upregulating genes such as mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy1 (Opa1), while inhibiting mitochondrial fission by regulating genes like dynamin-related protein 1 (Drp1) and Fission 1 (Fis1). Additionally, melatonin modulates autophagy, either enhancing or suppressing it depending on the cellular context, to maintain mitochondrial homeostasis and prevent oxidative damage. Melatonin is synthesized in various tissues, including the pineal gland, and can be transported into mitochondria. Its regulatory effects on mitochondrial function are essential for maintaining cellular energy supply and preventing mitochondrial-related diseases. The review highlights the potential of melatonin as a therapeutic agent for mitochondrial-related disorders, emphasizing the need for further research to fully understand its mechanisms and applications.