This review provides a comprehensive and systematic overview of mitochondrial quality control and its role in major diseases. It highlights three fundamental characteristics of mitochondrial quality control: morphology and dynamics, function and metabolism, and protein expression and regulation. The review extensively examines how imbalances in mitochondrial quality are linked to various diseases, including ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. Innovative approaches to target mitochondrial quality control, such as small molecule drugs, nanomolecular materials, and cellular therapies, are also explored. The review offers insights into the shared mechanisms underlying the occurrence and progression of major diseases and provides theoretical support and practical guidance for the development of therapeutic strategies targeting mitochondrial quality control.This review provides a comprehensive and systematic overview of mitochondrial quality control and its role in major diseases. It highlights three fundamental characteristics of mitochondrial quality control: morphology and dynamics, function and metabolism, and protein expression and regulation. The review extensively examines how imbalances in mitochondrial quality are linked to various diseases, including ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. Innovative approaches to target mitochondrial quality control, such as small molecule drugs, nanomolecular materials, and cellular therapies, are also explored. The review offers insights into the shared mechanisms underlying the occurrence and progression of major diseases and provides theoretical support and practical guidance for the development of therapeutic strategies targeting mitochondrial quality control.