This review provides a comprehensive and systematic overview of mitochondrial quality control and explores its potential for treating major diseases. Mitochondrial quality control involves three fundamental characteristics: morphology and dynamics, function and metabolism, and protein expression and regulation. Imbalances in mitochondrial quality are linked to major diseases such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. The review explores innovative approaches to target mitochondrial quality control, including small molecule drugs, nanomaterials, and novel cellular therapies. It also discusses the mechanisms underlying mitochondrial quality imbalances in various diseases and highlights the importance of mitochondrial quality control in disease progression. The review emphasizes the need for a deeper understanding of mitochondrial quality control to develop effective therapeutic strategies for major diseases.This review provides a comprehensive and systematic overview of mitochondrial quality control and explores its potential for treating major diseases. Mitochondrial quality control involves three fundamental characteristics: morphology and dynamics, function and metabolism, and protein expression and regulation. Imbalances in mitochondrial quality are linked to major diseases such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. The review explores innovative approaches to target mitochondrial quality control, including small molecule drugs, nanomaterials, and novel cellular therapies. It also discusses the mechanisms underlying mitochondrial quality imbalances in various diseases and highlights the importance of mitochondrial quality control in disease progression. The review emphasizes the need for a deeper understanding of mitochondrial quality control to develop effective therapeutic strategies for major diseases.