Abstract Body: An aortic aneurysm is a disease caused by the weakening of the vascular wall structure, leading to the dilation of the vessel. It most commonly occurs in the abdominal aorta and poses a high risk of aortic dissection or rupture. Surgical treatment is necessary to improve the prognosis of abdominal aortic aneurysms, as there are currently no effective drugs to treat or control the condition. The development of aortic aneurysms is closely associated with inflammatory responses and oxidative stress in the vascular wall. Ganoderma lucidum, a widely used traditional Chinese medicine, contains triterpenoids with antioxidant and anti-inflammatory properties. This study hypothesizes that Ganoderma lucidum and its triterpenoids can suppress abdominal aortic aneurysm formation through their antioxidant and anti-inflammatory properties. We found that Ganoderma lucidum has a therapeutic effect in maintaining the integrit y of the aortic wall. It effectively inhibited aortic aneurysm formation in mouse models induced by angiotensin II (Ang II) and calcium chloride (CaCl₂). Ganoderma lucidum protected vascular smooth muscle cells and reduced oxidative stress and inflammation in the vascular wall, thereby preserving the structure and elasticity of the vascular wall and inhibiting the development of aortic aneurysms. Mechanistically, in addition to observing the direct free radical-scavenging ability of Ganoderma triterpenoids, we discovered that these compounds protect smooth muscle cells by reducing the accumulation of reactive oxygen species and apoptotic responses caused by H₂O₂. This may occur through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genes, including heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), initiating cellular antioxidant effects. In summary, Ganoderma lucidum and its triterpenoids provide an effective therapeutic approach to mitigating aortic aneurysm formation by protecting vascular smooth muscle cells and maintaining the integrity of the aortic wall through their antioxidant effects.