Antifouling polymer have important implications for many applications ranging from biomedical devices to marine vessels. The most widely employed polymers are polyethylene glycol (PEG) for fouling resistant property and polydimethylsiloxane (PDMS) for fouling release property. Recent reports suggest that copolymers containing both PEG and PDMS may show synergistic effects, and the performance depends on the copolymer composition. Here, we develop copolymers containing PEG and PDMS by utilizing a reactive poly(pentafluorophenyl acrylate) (PPFPA). The PPFPA contains active PFP groups, thus it is utilized to prepare copolymers through simple substitution reaction. Copolymers with different PEG and PDMS ratios are prepared then tested against cells and proteins. In all scenarios tested, the copolymers are found to show better antifouling performance than PEG or PDMS homopolymer. Moreover, optimized copolymer composition is determined depending on the nature of the fouling organism.