Recently, the red blood cell (RBC) membrane has been used as a mimetic nanocoating for nanoparticles for drug delivery systems to promote their biocompatibility. In the present study, the nano-sized RBC membrane was coated on the surface of gene complexes through electrostatic interactions to prepare biomimetic gene delivery systems so as to improve their biocompatibility and prolong their circulation time in vivo. The structure of the biomimetic gene delivery systems was determined by transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). They exhibited low cytotoxicity and high transfection efficiency in endothelial cells (ECs), which could improve the migration ability of ECs. Besides, the biomimetic gene delivery systems exhibited strong immune evasion and long in vivo circulation time. The phagocytic rate of these biomimetic gene delivery systems reduced 52% compared with that of the PLGA-PEI/pZNF580 control group (without RBC membrane modification). Their circulation time in vivo was more than 2 times higher than that of the control group. Consequently, we provide a simple method for the preparation of camouflaged gene delivery systems, which can further facilitate the development of a gene delivery platform for the therapy of vascular diseases via enhancing EC transfection. This strategy will open up a new avenue for gene delivery systems by RBC membrane camouflage.