Mitochondria, traditionally known for their role in cellular energy production, have recently been recognized as secretory organelles that can be released into the extracellular space under both physiological and pathological conditions. These secreted mitochondria play diverse roles by regulating metabolism, immune response, and cell differentiation or maturation. Research has shown that local or systemic administration of mitochondria can have therapeutic effects in various disease models, leading to growing interest in their potential as therapeutic agents. This review discusses the emerging roles of mitochondria as extracellularly secreted organelles, focusing on their functions beyond energy production. It also provides an update on the therapeutic outcomes of mitochondrial transplantation in animal models and ongoing clinical trials, highlighting the potential of using mitochondria as a novel therapeutic intervention. The review covers the evidence, mechanisms, and biological effects of extracellular mitochondrial secretion, as well as the therapeutic effects of mitochondrial transplantation in conditions such as cardiac ischemia, cerebral ischemia, and inflammatory muscle diseases. Despite the promising results, many critical questions remain unanswered, particularly regarding the molecular mechanisms of mitochondrial secretion and transfer, target specificity, and the development of efficient mitochondrial transplantation protocols. Future research should aim to unravel these mechanisms and improve the efficiency and efficacy of mitochondrial transplantation therapy.Mitochondria, traditionally known for their role in cellular energy production, have recently been recognized as secretory organelles that can be released into the extracellular space under both physiological and pathological conditions. These secreted mitochondria play diverse roles by regulating metabolism, immune response, and cell differentiation or maturation. Research has shown that local or systemic administration of mitochondria can have therapeutic effects in various disease models, leading to growing interest in their potential as therapeutic agents. This review discusses the emerging roles of mitochondria as extracellularly secreted organelles, focusing on their functions beyond energy production. It also provides an update on the therapeutic outcomes of mitochondrial transplantation in animal models and ongoing clinical trials, highlighting the potential of using mitochondria as a novel therapeutic intervention. The review covers the evidence, mechanisms, and biological effects of extracellular mitochondrial secretion, as well as the therapeutic effects of mitochondrial transplantation in conditions such as cardiac ischemia, cerebral ischemia, and inflammatory muscle diseases. Despite the promising results, many critical questions remain unanswered, particularly regarding the molecular mechanisms of mitochondrial secretion and transfer, target specificity, and the development of efficient mitochondrial transplantation protocols. Future research should aim to unravel these mechanisms and improve the efficiency and efficacy of mitochondrial transplantation therapy.