ETHNOPHARMACOLOGICAL RELEVANCE: Chinese medicine, specifically Huangqi Chifeng Decoction (HQCF), is recognized for its efficacy in treating atherosclerosis (AS), a common cardiovascular disease. Despite its established benefits in addressing Qi deficiency, blood stasis, and collateral obstruction, the precise mechanism through which HQCF affects AS remains unclear. AIM OF THE STUDY: This study investigated the potential of HQCF to mitigate AS by suppressing smooth muscle cell (SMC) foam formation through the ferroptosis pathway. MATERIALS AND METHODS: An AS model was established using ApoE RESULTS: HQCF the pathological state of the aorta in ApoE CONCLUSION: These findings suggest that HQCF protects SMCs from ferroptosis by regulating the TXN/xCT/GPX4 pathway, ameliorating the aortic pathological state, alleviating oxidative stress, and maintaining mitochondrial homeostasis in mice.