<p>Atherosclerosis is a disease condition caused by accumulation of cholesterol-laden foam cells, leading to lipid plaque formation, narrowing, and impaired blood flow. Although current stent technologies are effective in restoring vessel patency and promoting endothelial repair, they largely fail to address the underlying pathological processes driving atherosclerosis, particularly buildup of lipid-laden foam cells and the abnormal migration and proliferation of vascular smooth muscle cells within the arterial wall. Recent strategies involving biodegradable stents eluting lipid-lowering agents such as Probucol and Succinobucol have shown promising results; however, adverse effects including thrombogenicity and fibrin deposition have limited their clinical utility. To address these challenges, using natural therapeutics that can mimic the lipid-lowering ability and target foam cells, we developed a bioresorbable stent functionalized with curcumin by covalently conjugating it onto a PLA/PCL stent via esterification, without compromising the stent’s mechanical integrity. The curcumin-conjugated PLA/PCL biodegradable stent (Cur-PLA/PCL) exhibited excellent hemocompatibility by significantly reducing fibrinogen adsorption, inhibiting platelet adhesion, and preventing thrombus formation simultaneously. Released curcumin showed strong antioxidant and anti-inflammatory effects by downregulating TNF-α, IL-1β, and IL-6, thereby fostering a regenerative microenvironment for endothelial cells. Furthermore, curcumin promoted cholesterol efflux from foam cells, resulting in ~ 70% reduction in intracellular lipid accumulation by day 7 through upregulation of ABCA1 and ABCG1 transporters. In addition, curcumin promoted selective apoptosis of foam cells via increased expression of FAS and BAX pathways. These findings demonstrate the potential of natural compound-functionalized stents as a promising platform for targeted and sustained atherosclerosis therapy.</p> Graphical Abstract <p></p>