Mitochondria, with their intricate functions and information processing, play a pivotal role in health regulation and disease progression. Mitochondrial dysfunctions are implicated in various common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. Despite the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction, mitochondria remain among the most important therapeutic targets. Recent years have seen the emergence and advancement of strategies targeting mitochondrial dysfunction, including preclinical trials of using healthy mitochondria to replenish or replace damaged ones. Mitochondrial components, such as mtDNA, microRNAs, and associated proteins, have shown potential as therapeutic agents in immunometabolic diseases and tissue injuries. This review provides a comprehensive overview of mitochondrial pathophysiology in common diseases, highlighting current strategies for treating mitochondrial dysfunction, including dietary supplements, pharmacological agents, and mitochondrial transplantation. It also discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment. Key points include: - Mitochondria's multifaceted roles in cellular activities, such as energy production, lipid metabolism, Ca2+ homeostasis, and apoptosis. - The concept of mitochondrial dysfunction and its relationship with cellular environment. - Advances in mitochondrial biology and therapeutic strategies, including gene replacement therapies and gene editing technologies. - The role of mitochondrial components in intercellular communication and their potential as therapeutic agents. - The importance of calcium homeostasis, energy and nutrient sensing, and innate immunity in mitochondrial function. - The historical development of mitochondrial research and the correlation between mitochondrial genetic anomalies and degenerative diseases. - Concrete examples of mitochondrial dysfunction in common diseases, such as ischemic/reperfusion injuries, neurodegeneration, and metabolic disorders. The review emphasizes the need for a deeper understanding of mitochondrial contributions to common pathologies to elucidate their roles in disease and to identify co-dependent therapeutic targets.Mitochondria, with their intricate functions and information processing, play a pivotal role in health regulation and disease progression. Mitochondrial dysfunctions are implicated in various common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. Despite the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction, mitochondria remain among the most important therapeutic targets. Recent years have seen the emergence and advancement of strategies targeting mitochondrial dysfunction, including preclinical trials of using healthy mitochondria to replenish or replace damaged ones. Mitochondrial components, such as mtDNA, microRNAs, and associated proteins, have shown potential as therapeutic agents in immunometabolic diseases and tissue injuries. This review provides a comprehensive overview of mitochondrial pathophysiology in common diseases, highlighting current strategies for treating mitochondrial dysfunction, including dietary supplements, pharmacological agents, and mitochondrial transplantation. It also discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment. Key points include: - Mitochondria's multifaceted roles in cellular activities, such as energy production, lipid metabolism, Ca2+ homeostasis, and apoptosis. - The concept of mitochondrial dysfunction and its relationship with cellular environment. - Advances in mitochondrial biology and therapeutic strategies, including gene replacement therapies and gene editing technologies. - The role of mitochondrial components in intercellular communication and their potential as therapeutic agents. - The importance of calcium homeostasis, energy and nutrient sensing, and innate immunity in mitochondrial function. - The historical development of mitochondrial research and the correlation between mitochondrial genetic anomalies and degenerative diseases. - Concrete examples of mitochondrial dysfunction in common diseases, such as ischemic/reperfusion injuries, neurodegeneration, and metabolic disorders. The review emphasizes the need for a deeper understanding of mitochondrial contributions to common pathologies to elucidate their roles in disease and to identify co-dependent therapeutic targets.