Peripheral artery disease (PAD), characterized by progressive occlusion of peripheral arteries, is a major global health concern associated with high risks of ischemic complications and limb dysfunction. Endovascular stenting remains a primary therapeutic approach; however, the development of biodegradable vascular stents that offer both sufficient mechanical resilience and antithrombotic, anti-restenotic surfaces remains challenging, especially in highly deformable peripheral vessels. Herein, a 3D-printed biodegradable drug-eluting stent (DES) based on biofunctional silica–polycaprolactone nanocomposites and Janus surface nanoengineering is presented. Sol–gel-derived silica incorporation and extrusion-based 3D printing yield stents with tuned radial strength, elliptical struts that reduce flow disturbance, and enhanced support for endothelial regeneration. Janus nanoengineering is achieved through tantalum (Ta) plasma immersion ion implantation. The resultant nano-Ta-enriched luminal surface promotes human umbilical vein endothelial cell adhesion and proliferation. Meanwhile, the abluminal layer, comprising sirolimus/poly-L-lactic acid and nano-Ta, suppresses vascular smooth muscle cell proliferation, reduces platelet thrombosis, and minimizes the initial burst release of therapeutic agents. Comprehensive in vitro hemocompatibility and cytocompatibility studies, combined with in vivo evaluation in a PAD model, demonstrate improved patency, reduced neointimal hyperplasia, and favorable tissue responses. This 3D-printed, Janus-engineered DES represents a promising theragenerative platform for vascular tissue engineering.