Post-implantation infections are one of the major issues curtailing the clinical performance of numerous biomedical devices, leading to implant failure. With the advancement of modern surgery, improvement of implant surfaces is highly desirable to address biomaterial-associated biofilm formation. Herein, we report a photo-crosslinkable polymeric coating material composed of dimethacrylate end-terminated polylactic acid (PLA)/polyethylene glycol (PEG) diblock copolymers (PLEGDA) bequeathed with ZnO nanoparticles (NPs) for the surface modification of biomaterials via a facile photo-grafting method. Incorporation of 1 wt% ZnO NPs to the as-synthesized PLEGDA bestows the surface with potential contact-killing antibacterial properties against S. aureus and E. coli bacteria. The suitable hydrophobic/hydrophilic balance of PLA8600/PEG2000 segments in combination with ZnO NPs offers low fouling against both bacteria, with superior resistance against E. coli. Moreover, the homogeneous coating exhibits excellent biocompatibility as indicated by in vitro cell viability and cell adhesion behavior. Therefore, ZnO NPs-embedded biocompatible polymer-based, low-fouling, UV-assisted coating has great potential in the surface modification of different biomaterials for combatting implant-associated infections while preventing multiple drug resistance.