Preventing bacterial colonization and thrombotic adhesion is a major challenge for implantable medical devices, as early biofouling often leads to infection and thrombus formation. Here, we developed a zwitterion-conjugated glycol chitosan (GC-ZW) coating designed to suppress bacterial biofouling and platelet adhesion on biomedical substrates. A sulfobetaine zwitterion was grafted onto glycol chitosan via aza-Michael addition to form a hydrophilic polymer capable of forming a hydration-rich interface. GC-ZW was immobilized on surfaces through a coordination-driven layer-by-layer assembly using tannic acid and Zr (IV) ions, producing stable coatings. Compared with unmodified substrates, GC-ZW–coated surfaces showed significantly reduced adhesion of E. coli and platelets. This work provides a stable coating strategy for biomedical surfaces and offers a practical approach to mitigating infection- and thrombosis-related risks.