Skeletal muscle, one of the most abundant tissues in the human body, plays a crucial role in motor function, energy metabolism, immune regulation, and the aging process. The skeletal muscle tissue microenvironment is highly complex, involving a variety of cell types, a three-dimensional architecture, and specific mechanical properties. Replicating these intricate features in vitro to create a biomimetic skeletal muscle model has long posed significant challenges. The advent of organ-on-a-chip technology, which integrates microfluidics with 3D cell culture, offers a groundbreaking approach to faithfully replicate the key structural and functional characteristics of human skeletal muscle tissue. The organ-on-a-chip technology enables precise control over the microenvironment, facilitating the study of skeletal muscle development, disease progression, and drug screening in a highly controlled in vitro setting. The skeletal muscle-on-a-chip (SMoC) has been utilized to investigate a variety of muscle-related diseases, including Duchenne muscular dystrophy and amyotrophic lateral sclerosis, offering valuable insights into disease mechanisms and potential therapeutic strategies. Additionally, SMoC serves as a powerful tool for testing the efficacy and toxicity of new drugs, as well as exploring tissue repair and regeneration techniques. Recent advances in the design and fabrication of SMoCs have further enhanced their physiological relevance, including the incorporation of anisotropic scaffolds to guide muscle fiber alignment and the use of electrical and mechanical stimulation to mimic the native muscle environment. These improvements have led to more accurate disease models and more reliable drug testing platforms, making SMoC a versatile and promising tool in biomedical research. In the end, the prospects and challenges facing the future development of SMoC were discussed. Currently, SMoC still exhibit limitations in terms of cell sources and functionalities. However, the integration with emerging technologies such as gene editing and biosensing in the future could pave the way for significant advancements and breakthroughs. The development of SMoC is expected to further promote the process of translational medicine, with potential applications extending beyond basic research into clinical settings, where it could revolutionize personalized medicine, regenerative therapy and precision drug development.