Angioplasty with stents is the most important method for the treatment of coronary artery disease (CAD). However, the drug-eluting stents (DES) that are widely used have the increased risks of inflammatory reactions and late stent thrombosis (LST) because of the persistence of the polymer coatings. To improve the biosafety, a novel polymer-free-composite drug-eluting coating composed of magnetic mesoporous silica nanoparticles (MMSNs) and carbon nanotubes (CNTs) was constructed using the electrophoretic deposition (EPD) method in this study. A crack-free two-layered coating with impressive network nanotopologies was successfully obtained by regulating the composition and structures. This nanostructured coating exhibits excellent mechanical flexibility and blood compatibility in vitro, and the drug-loading and release performance is satisfactory as well. The in vivo study shows that this composite coating has the obvious advantage of rapid endothelialization because of its unique 3D nanostructured topology in comparison with the commercial polymer-coated DES. This study aims to provide new ideas and reliable data to design novel functional coatings that could accelerate the re-endothelialization process and avoid inflammatory reactions, thus improving the in vivo biosafety of DES.