Abstract: Atherosclerosis (AS) is a cardiovascular disease characterized by chronic inflammation and abnormal vascular structure, posing a significant threat to global public health. In the pathogenesis of AS, autophagy plays a dual role: it stabilizes AS plaques by clearing reactive oxygen species (ROS), degrading lipid bodies, and inhibiting excessive proliferation and migration of vascular smooth muscle cells (VSMCs). However, excessive or aberrant autophagy may lead to apoptosis or necrosis of endothelial cells and VSMCs, thereby increasing the risk of thrombosis. Irisin, a myokine secreted by skeletal muscle, exerts important regulatory effects on the development of AS via autophagy. Specifically, irisin mitigates atherosclerosis progression through autophagy-dependent mechanisms, either directly or indirectly, by regulating cholesterol metabolism, suppressing inflammation, inhibiting excessive VSMC proliferation, and modulating pyroptosis, among other mechanisms. The involvement of irisin in the pathological process of atherosclerosis through autophagy provides a theoretical foundation for exploring novel therapeutic strategies.