In this work, a slippery liquid-infused silver-polytetrafluoroethylene (AgFP) coating was fabricated via a spontaneous polycondensation of 1H,1H,2H,2H-perfluorooctyltriethoxysilane (PFOTES) onto an electroless AgF sublayer. The AgFP coating demonstrated great stability and superior repellence against liquids with a wide range of surface tensions. The anti-biofouling properties were investigated by adsorption of Escherichia coli, Staphylococcus aureus, fibrinogen, and bovine serum albumin. Owing to the self-cleaning property, the AgFP demonstrated enhanced anti-adhesion activity against both bacteria and proteins relative to traditional electroless coatings, despite the fibrinogen deposition significantly promoting bacterial binding. While its ultra-low surface energy was not within the optimum surface energy region for minimum bacterial or protein adhesion, the AgFP coating still displayed excellent anti-biofilm capability in a protein-bacteria co-deposition model, reducing over 80% of BSA-supplemented biomass coverage on Ag surfaces and over 60% of Fgn-supplemented biomass coverage on AgF surfaces, respectively. To understand the anti-adhesion mechanism, the XDLVO model was used to explain the adhesion behaviour of both bacteria and proteins. Cytotoxicity assays confirmed that the AgFP coating had good biocompatibility with fibroblast cells. The results from this research provide attractive prospects for the application of the AgFP coating in biomedical devices to combat infections.