Atherosclerosis, resulting from chronic inflammation of the arterial wall, serves as the underlying cause of multiple major cardiovascular diseases. Current anti-inflammatory therapies often exhibit limited and unsatisfactory efficacy. To address this, we have designed a selenium-doped copper formate (Cuf-Se) nanozyme for the treatment of atherosclerosis, which possesses superoxide dismutase (SOD) and glutathione peroxidase (GPx)-like activities. The Cuf-Se can efficiently scavenge reactive oxygen species (ROS), inhibit cellular senescence, and prevent the formation of foam cells. It acts on macrophages to reduce cellular ROS levels and lipid oxidation, thereby significantly inhibiting inflammation-related processes. Notably, while inhibiting foam cell formation, Cuf-Se also alleviates endothelial cells senescence. After intravenous administration, Cuf-Se effectively inhibits the formation of atherosclerosis in mice through the synergistic effects of antisenescence and antioxidant properties, reducing plaque area by approximately 5-fold. This study provides an effective strategy for the treatment of atherosclerosis.