Mussel-inspired polyphenolic chemistry provides a versatile platform for multifunctional biomaterials. Polydopamine, a catechol-rich nanoscale coating, forms spontaneously on diverse substrates and serves as a universal primer, with assembly driven by cation–π interactions from biological catecholamines. Building on this, chitosan–catechol conjugates act as coagulopathy-independent hemostats, inducing rapid clotting via polyphenol–protein complexation, validated from preclinical models to a first-in-human trial. Tannic acid–modified proteins and peptides preferentially accumulate in the heart, enhancing local retention of cardioprotective agents. Polyphenol interactions with keratin and follicular proteins also strengthen hair anchorage and modulate the scalp microenvironment for hair loss mitigation. These studies highlight mussel-inspired polyphenols as a unifying toolbox for next-generation adhesive and pharmaceutical biomaterials.