We have synthesized and characterized a novel zwitterionic nanocomposite hydrogel as effective chronic wound healing dressings. The hydrogel is composited of nonfouling zwitterionic polymer as a major composition, plus small quantity of nano-sized clay for improved mechanical strength and in-situ formation silver nanoparticles for antimicrobial function. The novel zwitterionic nanocomposite hydrogel possesses unique features, including 1. biocmpatibility; 2. high water content; 3. anti-biofouling properties; 4. strong durability; 5. suppression of bacterial growth; 6. controlled release of Ag ions. These features allow developed formulation becoming extraordinary chronic wound dressing for clinical applications.The hydrogel was fabricated via a “onepot synthesis” approach and the physicochemical properties were characterized detail. Moreover, the antifouling properties of hydrogels were evaluated in contact with a protein and bacterial solutions.