Skeletal muscle is widely recognized as an endocrine organ capable of synthesizing and secreting various cytokines and peptides collectively known as myokines. These myokines play a crucial role in the communication between muscle and other organs, including adipose tissue, liver, pancreas, bone, and brain. Research indicates that physical activity can stimulate the production of myokines in skeletal muscle, which then impact various organ functions through autocrine, paracrine, and endocrine pathways. Myokines contribute to the health benefits associated with exercise, including improved cognitive function, regulation of lipid and glucose metabolism, and promotion of muscle and bone development. Although our understanding of the specific functions of myokines in humans is still limited, their potentials as biomarkers for monitoring exercise programs and managing chronic diseases are significant. In summary, this study reviews the types and functions of myokines, as well as the effects of exercise on their expression, emphasizing the potential importance of skeletal muscle as an endocrine organ in promoting health and preventing chronic diseases. Additionally, it highlights the clinical significance of recognizing skeletal muscle as an endocrine organ and provides new insights for future research directions.