Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration, leading to increased fracture risk. Mitochondrial dysfunction is emerging as a crucial factor in the pathogenesis of OP, affecting the delicate balance between bone formation and resorption. This review explores the correlation between mitochondrial dysfunction and OP, including alterations in mitochondrial DNA (mtDNA), impaired oxidative phosphorylation (OXPHOS), dysregulation of mitophagy, defects in mitochondrial biogenesis and dynamics, and excessive reactive oxygen species (ROS) accumulation. The review also discusses potential therapeutic strategies for modulating mitochondrial function to treat OP, such as targeting OPA1, PINK, sirtuins, and mitochondrial-derived peptides. While some strategies show promise, further research is needed to validate their safety and efficacy in clinical settings. The potential for establishing effective and safe therapeutic approaches for OP from a mitochondrial perspective is promising.Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration, leading to increased fracture risk. Mitochondrial dysfunction is emerging as a crucial factor in the pathogenesis of OP, affecting the delicate balance between bone formation and resorption. This review explores the correlation between mitochondrial dysfunction and OP, including alterations in mitochondrial DNA (mtDNA), impaired oxidative phosphorylation (OXPHOS), dysregulation of mitophagy, defects in mitochondrial biogenesis and dynamics, and excessive reactive oxygen species (ROS) accumulation. The review also discusses potential therapeutic strategies for modulating mitochondrial function to treat OP, such as targeting OPA1, PINK, sirtuins, and mitochondrial-derived peptides. While some strategies show promise, further research is needed to validate their safety and efficacy in clinical settings. The potential for establishing effective and safe therapeutic approaches for OP from a mitochondrial perspective is promising.