The challenges for clinical application of small-diameter vascular graft are mainly acute/chronic thrombosis, inadequate endothelialization, intimal hyperplasia caused by inflammation, oxidative stress, and the mismatch of mechanical compliance after transplantation. How to construct an effective regenerative microenvironment through a material with uniform dispersion of active components is the premise of maintaining patency of a vascular graft. In this study, we have compounded poly(ester-urethane)urea (PEUU) with various optimized concentrations of resveratrol (Res) by homogeneous emulsion blending, followed by electrospinning into the hybrid PEUU/Res nanofibers (P/R-0, P/R-0.5, P/R-1.0, and P/R-1.5). Then the microstructure, surface wettability, mechanical properties, degradation, Res sustained release properties, hemocompatibility, and cytocompatibility of P/R were evaluated comprehensively. The results indicate that Res can be gradually released from the P/R, and both the hydrophilicity and antioxidant ability of the nanofiber gradually increase with the increase of Res content. Moreover, with the increase of Res, the viability and proliferation behavior of HUVECs were significantly improved. Meanwhile, tube formation and migration experiments showed that Res promoted the formation of a neovascularization network. In brief, it is concluded that P/R-1.0 is the optimal candidate with a uniform microstructure, moderate wettability, optimized mechanical properties, reliable hemocompatibility and cytocompatibility, and strongest ability to promote endothelial growth for the vascularizing matrix.