Surface biomimetic modification with extra-cellular matrix (ECM)-derived biomolecules is an emerging potential method of accelerating the healing of vascular stent lesions. However, insufficient capacity of the constructed biofunctional layer in maintaining its long-term efficiency and preventing thrombus and neointimal hyperplasia continue to be major limitations in clinical application. On the basis of the structure and function of ECM, in this study, we constructed a novel stromal cell-derived factor-1α (SDF-1α)/laminin-loaded nanocoating on the 316L stainless steel (SS) surface to provide improved function in modulation of vascular remodeling. The modified surface was found to control delivery of biomolecules and exhibit promising potential to provide stage-adjusted treatment after injury. An in vitro biocompatibility study suggested that the constructed layer may effectively prevent thrombosis formation by inhibiting platelet adhesion and activation, while accelerating endothelium regeneration by inducing endothelial cell (EC) migration and endothelial progenitor cell (EPC) aggregation. An in vivo animal test further demonstrated that the nanocoating may prevent thrombus and neointimal hyperplasia after implantation for 3 months. Therefore, the ECM-inspired nanocoating described in this study is a promising novel approach for vascular stent surface modification.