This review explores the role of mitochondrial dysfunction in osteoporosis (OP) and potential therapeutic strategies. Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration, leading to increased fracture risk. It arises from an imbalance between bone resorption and formation. Mitochondrial dysfunction is a key factor in OP pathogenesis, as mitochondria regulate bone homeostasis by maintaining the balance between bone formation and resorption. Mitochondrial dysfunction leads to reduced ATP synthesis, increased reactive oxygen species (ROS), and impaired mitochondrial function, contributing to bone loss. Mitochondrial DNA (mtDNA) mutations, oxidative phosphorylation (OXPHOS) impairment, mitophagy dysregulation, and excessive ROS accumulation are associated with OP. Mitochondrial dysfunction also affects bone cell function, impairing osteoblast activity and enhancing osteoclast resorption. Mitochondrial biogenesis and dynamics are crucial for maintaining bone homeostasis, and their disruption contributes to OP. Mitophagy is essential for removing damaged mitochondria and maintaining mitochondrial quality. Therapeutic strategies targeting mitochondrial function, such as modulating OPA1, PINK, Sirtuins, and mitochondrial-derived peptides, show promise in treating OP. These approaches aim to enhance mitochondrial function, reduce ROS, and restore bone homeostasis. However, further research is needed to validate their efficacy and safety in clinical settings.This review explores the role of mitochondrial dysfunction in osteoporosis (OP) and potential therapeutic strategies. Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration, leading to increased fracture risk. It arises from an imbalance between bone resorption and formation. Mitochondrial dysfunction is a key factor in OP pathogenesis, as mitochondria regulate bone homeostasis by maintaining the balance between bone formation and resorption. Mitochondrial dysfunction leads to reduced ATP synthesis, increased reactive oxygen species (ROS), and impaired mitochondrial function, contributing to bone loss. Mitochondrial DNA (mtDNA) mutations, oxidative phosphorylation (OXPHOS) impairment, mitophagy dysregulation, and excessive ROS accumulation are associated with OP. Mitochondrial dysfunction also affects bone cell function, impairing osteoblast activity and enhancing osteoclast resorption. Mitochondrial biogenesis and dynamics are crucial for maintaining bone homeostasis, and their disruption contributes to OP. Mitophagy is essential for removing damaged mitochondria and maintaining mitochondrial quality. Therapeutic strategies targeting mitochondrial function, such as modulating OPA1, PINK, Sirtuins, and mitochondrial-derived peptides, show promise in treating OP. These approaches aim to enhance mitochondrial function, reduce ROS, and restore bone homeostasis. However, further research is needed to validate their efficacy and safety in clinical settings.