Mitochondria, crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism and various vital life processes. The sophisticated mitochondrial quality control (MQC) mechanism, encompassing mitochondrial biogenesis, dynamics, and mitophagy, has gained increasing attention for its molecular mechanisms. This review provides a comprehensive overview of the primary mechanisms and functions of key regulators involved in MQC components. It also details the critical physiological functions regulated by MQC and its diverse roles in various systemic diseases, including cancer, cardiovascular disease, metabolic disorders, neurological disorders, respiratory diseases, renal diseases, and digestive diseases. Additionally, the potential therapeutic and research prospects of targeting MQC to enhance mitochondrial function are discussed. The review highlights the importance of understanding the complex mechanisms of MQC to develop innovative strategies for mitigating mitochondrial dysfunction and associated pathologies.Mitochondria, crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism and various vital life processes. The sophisticated mitochondrial quality control (MQC) mechanism, encompassing mitochondrial biogenesis, dynamics, and mitophagy, has gained increasing attention for its molecular mechanisms. This review provides a comprehensive overview of the primary mechanisms and functions of key regulators involved in MQC components. It also details the critical physiological functions regulated by MQC and its diverse roles in various systemic diseases, including cancer, cardiovascular disease, metabolic disorders, neurological disorders, respiratory diseases, renal diseases, and digestive diseases. Additionally, the potential therapeutic and research prospects of targeting MQC to enhance mitochondrial function are discussed. The review highlights the importance of understanding the complex mechanisms of MQC to develop innovative strategies for mitigating mitochondrial dysfunction and associated pathologies.