There is a critical need for modular, scalable biosensing technologies capable of detecting diverse targets in complex clinical and environmental matrices. This work presents two complementary electrochemical platforms that integrate synthetic protein engineering and bio-electrocatalytic material design to address this challenge. In one approach, synthetic binding proteins called monobodies were chemically modified and immobilized on electrodes using NHS–EDC coupling. This enabled the detection of clinically relevant biomarkers like lysozyme through direct electrochemical signaling, demonstrating the potential for compact, customizable diagnostic sensors. A complementary strategy focuses on improving electrocatalytic performance in enzyme-based systems, which often face challenges with inefficient electron transfer. To address this, metal–phenolic network (MPN) coatings were developed by combining natural polyphenols with transition metal ions and co-polymerizing them with redox enzymes on electrode surfaces. These coatings significantly enhance catalytic current and electron transfer efficiency, particularly in multi-enzyme cascade reactions. Together, these separate but complementary platforms show promise to advance biosensing and electrocatalysis, offering flexible solutions for diagnostics, environmental monitoring, and analytical applications