The surface chemistry of the scaffolds plays vital role in regulating cell behavior in the tissue engineering. In order to enhance the biocompatibility of the polycaprolactone (PCL) scaffolds, a mussel-inspired modification and multiple bioactive molecules grafting method was developed. The modification method contained coating and polymerization of dopamine, the immobilization of bioactive molecules arginine-glycine-aspartic acid (RGD), and heparin. Fourier transform infrared spectroscopy (FTIR) results verified the successful polydopamine (PDA) coating and heparin grafting on the PCL scaffolds. Scanning electron microscope (SEM) and water contact angle tests verified the modification not only increased the nanofiber surface roughness, but also efficiently enhanced their surface wettability. Moreover, human umbilical vein endothelial cells (HUVECs) showed enhanced cell attachment, higher cell viability and greater cell proliferation on the RGD immobilized PCL electrospun nanofibers, which indicated great application prospect of this green method in the tissue engineering fields.