Mitochondrial transplantation is a promising therapeutic approach for the treatment of mitochondrial diseases caused by mutations in mitochondrial DNA, as well as several metabolic and neurological disorders. Animal studies have shown that mitochondrial transplantation can improve cellular energy metabolism, restore mitochondrial function, and prevent cell death. However, challenges need to be addressed, such as the delivery of functional mitochondria to the correct cells in the body, and the long-term stability and function of the transplanted mitochondria. Researchers are exploring new methods for mitochondrial transplantation, including the use of nanoparticles or CRISPR gene editing. Mechanisms underlying the integration and function of transplanted mitochondria are complex and not fully understood, but research has revealed some key factors that play a role. While the safety and efficacy of mitochondrial transplantation have been investigated in animal models and human trials, more research is needed to optimize delivery methods and evaluate long-term safety and efficacy. Clinical trials using mitochondrial transplantation have shown mixed results, highlighting the need for further research in this area. In conclusion, although mitochondrial transplantation holds significant potential for the treatment of various diseases, more work is needed to overcome challenges and evaluate its safety and efficacy in human trials. [BMB Reports 2023; 56(9): 488-495].