This review explores the mechanisms and physical activities involved in bone-skeletal muscle crosstalk. Bone and skeletal muscle work together to maintain musculoskeletal function, with skeletal muscle contraction driving bone movement and bone providing attachment sites for muscle. Exercise promotes bone strength and secretes osteocalcin and IGF-1 into the blood, improving muscle quality. Exercise also promotes myostatin, IL-6, irisin, and apelin into the blood, which act on bones to maintain bone balance. There is a special regulatory axis between myokines and osteokines, mainly influenced by exercise. Exercise affects important factors in bone-muscle interaction, which strengthen the connection between organs and are important for the diagnosis, prevention, and treatment of osteoporosis and sarcopenia. The review discusses the regulation of bone by muscle-derived factors, including myostatin, irisin, and IL-6. Myostatin inhibits muscle and bone growth, while irisin promotes bone formation and resorption. IL-6 influences bone metabolism and is involved in the regulation of bone and muscle. The review also discusses the regulation of muscle by bone-derived factors, including OCN, IGF-1, and sclerostin. OCN promotes muscle function and energy metabolism, IGF-1 promotes muscle growth and bone formation, and sclerostin inhibits bone formation. The review highlights the importance of exercise in bone-skeletal muscle crosstalk, as it enhances the interaction between bone and muscle, improves bone strength and muscle quality, and contributes to the diagnosis, prevention, and treatment of osteoporosis and sarcopenia. The review also discusses the need for further research on the mechanisms of bone-skeletal muscle crosstalk, including the role of exerkines, the regulation of bone and muscle by factors, and the effects of different micro-environments on tissue interaction. The review concludes that exercise is an important non-drug intervention for bone and muscle diseases, and that further research is needed to fully understand the mechanisms of bone-skeletal muscle crosstalk.This review explores the mechanisms and physical activities involved in bone-skeletal muscle crosstalk. Bone and skeletal muscle work together to maintain musculoskeletal function, with skeletal muscle contraction driving bone movement and bone providing attachment sites for muscle. Exercise promotes bone strength and secretes osteocalcin and IGF-1 into the blood, improving muscle quality. Exercise also promotes myostatin, IL-6, irisin, and apelin into the blood, which act on bones to maintain bone balance. There is a special regulatory axis between myokines and osteokines, mainly influenced by exercise. Exercise affects important factors in bone-muscle interaction, which strengthen the connection between organs and are important for the diagnosis, prevention, and treatment of osteoporosis and sarcopenia. The review discusses the regulation of bone by muscle-derived factors, including myostatin, irisin, and IL-6. Myostatin inhibits muscle and bone growth, while irisin promotes bone formation and resorption. IL-6 influences bone metabolism and is involved in the regulation of bone and muscle. The review also discusses the regulation of muscle by bone-derived factors, including OCN, IGF-1, and sclerostin. OCN promotes muscle function and energy metabolism, IGF-1 promotes muscle growth and bone formation, and sclerostin inhibits bone formation. The review highlights the importance of exercise in bone-skeletal muscle crosstalk, as it enhances the interaction between bone and muscle, improves bone strength and muscle quality, and contributes to the diagnosis, prevention, and treatment of osteoporosis and sarcopenia. The review also discusses the need for further research on the mechanisms of bone-skeletal muscle crosstalk, including the role of exerkines, the regulation of bone and muscle by factors, and the effects of different micro-environments on tissue interaction. The review concludes that exercise is an important non-drug intervention for bone and muscle diseases, and that further research is needed to fully understand the mechanisms of bone-skeletal muscle crosstalk.