Nowadays, small-diameter vascular grafts are attracting considerable interest in tissue engineering and are in great demand in clinical trials. However, the defect of weak patency limits the application of smallcaliber vessels in the coronary artery and peripheral vessel bypass graft surgery. Research shows that puerarin can protect endothelial cells from damage caused by inflammation, oxidative stress, and apoptosis. Simultaneously, puerarin can promote endothelial cell proliferation and differentiation. In this study, puerarin-loaded vascular grafts were made through coaxial electrospinning with gelatin by taking poly(L-lactic acid) as the carrier material and multiwalled carbon nanotubes as reinforced materials. The results showed that the resultant fibers have a core−shell structure with enhanced hydrophilicity, hydrophobicity, mechanical properties, and degradability, which are in good agreement with the properties of natural blood vessels. Compared with the commercially available puerarin drugs, the drug release cycle of the as-prepared puerarin-loaded core−shell structure fiber is effectively prolonged and highly efficient. Moreover, the biocompatibility test showed that the fiber that contains puerarin has no toxicity and side effects on endothelial cells, will not cause hemolysis, and meets the national safety regulations for medical materials.