Musculoskeletal disorders are common complications of sports injuries and age-related degeneration that negatively affect motor function and quality of life.Therefore,identification and screening of novel intervention targets are crucial for the rehabilitation and treatment of musculoskeletal disorders.Current research has indicated that the mechanosensitive channel Piezo1 regulates the metabolic homeostasis of the musculoskeletal system, including satellite cells, bones,tendons, and intervertebral discs, through multiple signaling cascades and molecular mechanisms. Moreover, Piezo1 is involved in the pathogenesis of musculoskeletal disorders, thereby emerging as a potential target for therapeutic intervention. In this article, we systematically discuss the microstructure, molecular regulatory network, and specific agonists and antagonists of Piezo1, as well as its functional roles in skeletal muscles, bones, tendons, and intervertebral discs, aiming to provide novel intervention targets and a theoretical basis for the rehabilitation and treatment of musculoskeletal disorders.