We engineer enzyme-functionalized surfaces for virtually any substrate and use case – medical devices, food-contact and packaging, membranes and sensors, textiles and films, process equipment and high-touch surfaces. Our modular design combines matrix-degrading enzymes to disperse biofilms, lytic enzymes to eliminate target organisms, and oxidoreductases that generate microbicidal H2O2 directly at the interface. We have e.g. demonstrated covalent grafting of cellobiose dehydrogenase (CDH) onto plasma-activated silicone (PDMS) with 60% fewer viable S. aureus after 3 h, ~70% less biofilm after 7 days, and 20% retained activity after 16 days in artificial urine, with no mammalian cell toxicity – evidence for durable, non-leaching performance. We also developed an ultrasound one-step deposition of active CDH nanoparticles that produce micromolar H2O2 and significantly reduce surface colonization, supporting scalable coating on polymers and other materials. Because CDH accepts a broad range of oligosaccharides – including components of bacterial exopolysaccharides – the system can self-activate where microbes adhere. Together with established immobilization chemistries (covalent grafting, layer-by-layer, entrapment/adsorption), this enables tailored integration across metals, polymers, glass, ceramics, and textiles.