Complete endothelialization is highly important for maintaining long-term patency and avoiding subsequent complications in implanting cardiovascular stents. It not only refers to endothelial cells (ECs) fully covering the inserted stents, but also includes the newly formed endothelium, which could exert physiological functions, such as anti-thrombosis and anti-stenosis. Clinical outcomes have indicated that endothelial dysfunction, especially the insufficiency of antithrombotic and barrier functions, is responsible for stent failure. Learning from vascular pathophysiology, endothelial dysfunction on stents is closely linked to the microenvironment of ECs. Evidence points to inflammatory responses, oxidative stress, altered hemodynamic shear stress, and impaired endothelial barrier affecting the normal growth of ECs, which are the four major causes of endothelial dysfunction. The related molecular mechanisms and efforts dedicated to improving the endothelial function are emphasized in this review. From the perspective of endothelial function, the design principles, advantages, and disadvantages behind current stents are introduced to enlighten the development of new-generation stents, aiming to offer new alternatives for restoring endothelial function.