Mitochondria, traditionally viewed as energy-producing organelles, are now recognized as secreted into the extracellular space under physiological and pathological conditions. These secreted mitochondria regulate metabolism, immune response, and cell differentiation in target cells. Research shows that mitochondrial transplantation can have therapeutic effects in various disease models, leading to interest in their potential as therapeutic agents. This review discusses the roles of mitochondria as extracellular secretory organelles and their therapeutic applications. Mitochondria are secreted through mechanisms such as microvesicles, CD38/cADPR/calcium signaling, actin polymerization, and changes in mitochondrial morphology. These secreted mitochondria can modulate recipient cell metabolism, immune responses, and differentiation. For example, mitochondrial transfer from mesenchymal stem cells enhances macrophage oxygen consumption, while mitochondrial transfer from astrocytes improves neuronal ATP levels. Mitochondria can also trigger anti-inflammatory or pro-inflammatory responses in recipient cells, depending on their cargo and the cellular context. Mitochondrial transplantation has shown promise in animal models of cardiac and cerebral ischemia, skeletal muscle dysfunction, and inflammatory diseases. Local or systemic delivery of isolated mitochondria has improved tissue function and reduced inflammation. Clinical trials are ongoing to evaluate the safety and efficacy of mitochondrial transplantation in conditions such as myocardial ischemia, cerebral ischemia, and inflammatory muscle diseases. The review highlights the potential of mitochondria as therapeutic agents, emphasizing the need for further research into the mechanisms of mitochondrial secretion, transfer, and their biological effects. Future studies should focus on improving the purity and stability of isolated mitochondria, optimizing transplantation protocols, and understanding the molecular mechanisms that govern their secretion and function. The development of mitochondrial-based therapies could offer new approaches for treating a range of diseases.Mitochondria, traditionally viewed as energy-producing organelles, are now recognized as secreted into the extracellular space under physiological and pathological conditions. These secreted mitochondria regulate metabolism, immune response, and cell differentiation in target cells. Research shows that mitochondrial transplantation can have therapeutic effects in various disease models, leading to interest in their potential as therapeutic agents. This review discusses the roles of mitochondria as extracellular secretory organelles and their therapeutic applications. Mitochondria are secreted through mechanisms such as microvesicles, CD38/cADPR/calcium signaling, actin polymerization, and changes in mitochondrial morphology. These secreted mitochondria can modulate recipient cell metabolism, immune responses, and differentiation. For example, mitochondrial transfer from mesenchymal stem cells enhances macrophage oxygen consumption, while mitochondrial transfer from astrocytes improves neuronal ATP levels. Mitochondria can also trigger anti-inflammatory or pro-inflammatory responses in recipient cells, depending on their cargo and the cellular context. Mitochondrial transplantation has shown promise in animal models of cardiac and cerebral ischemia, skeletal muscle dysfunction, and inflammatory diseases. Local or systemic delivery of isolated mitochondria has improved tissue function and reduced inflammation. Clinical trials are ongoing to evaluate the safety and efficacy of mitochondrial transplantation in conditions such as myocardial ischemia, cerebral ischemia, and inflammatory muscle diseases. The review highlights the potential of mitochondria as therapeutic agents, emphasizing the need for further research into the mechanisms of mitochondrial secretion, transfer, and their biological effects. Future studies should focus on improving the purity and stability of isolated mitochondria, optimizing transplantation protocols, and understanding the molecular mechanisms that govern their secretion and function. The development of mitochondrial-based therapies could offer new approaches for treating a range of diseases.