This account presents a general method for the construction of polymeric surface binders for digestion enzymes. Two prominent parts, namely, the modification of the copolymer composition and the screening assay for the most powerful inhibitors are both amenable to parallelization. The concept hinges on the appropriate selection of amino-acid-selective comonomers, their free radical copolymerization, and subsequent screening of the resulting copolymer library for efficient enzyme inhibition. A microscale synthetic procedure for the copolymerization process was developed, which produces water-soluble affinity polymers that can be stored for years at room temperature. Initial parallel screening was conducted in standard enzyme assays to identify polymeric inhibitors, which were subsequently subjected to determination of IC50 values for their target enzyme. For all digestion enzymes, except elastase, a number of polymer inhibitors were found, some of which were selective toward one or two protein targets. Since the key monomers of the best inhibitors bind to amino acid residues in the direct vicinity of the active site, we conclude that efficient coverage of the immediate environment by the copolymers is critical. Strong interference with enzymatic activity is brought about by blocking the substrate access and product exit to and from the active site.