An aortic aneurysm is a vascular disease characterized by a permanent dilation of arteries, which most commonly occurs in the infrarenal abdominal and ascending aortic regions in humans, life-threatening due to high risk of rupture. Currently, the treatment of aortic aneurysms has been limited to surgical intervention, with no effective therapeutic drugs having been found. Therefore, to find effective therapeutic targets has become a significant concern. Recent studies have shown that vascular endothelial cells can contribute to aortic aneurysms due to oxidative stress, inflammation, and the disruption of the endothelial barrier function. As the gradual revelation of the vital role of endothelial cells in aortic aneurysms, remarkable progress has been made on the investigation of the endothelial cells as the potential target for aortic aneurysm treatment. In this review, we focused on the mechanism by which endothelial cells are involved in the development and progression of aortic aneurysms as well as therapies targeting endothelial cells for aortic aneurysm treatment, thereby providing novel evidence for clinical intervention of aneurysm progression.