Mucus supports human health by hydrating, lubricating, and preventing infection of wet epithelial surfaces. The beneficial material properties and bioactivity of mucus stem from glycoproteins called mucins, motivating the development of mucin-derived hydrogels for wound dressings and antifouling coatings. However, these applications require robust gelation and adhesion to a wide range of substrates. Inspired by the chemical cross-linking and water-tolerant adhesion of marine mussel adhesive structures, we use catechol–thiol bonding to drive gelation of native mucin proteins and synthetic mucin-inspired polymers, forming soft, adhesive hydrogels that can be coated onto diverse surfaces. The gelation dynamics and adhesive properties can be systematically tuned by varying the hydrogel composition, polymer architecture, and thiol availability, with gelation timescales adjustable from seconds to hours, and values of elastic modulus, failure stress, and debonding work spanning orders of magnitude. We demonstrate the functionality of these gels in two applications: as tissue adhesives, using porcine skin as a proxy for human skin, and as bioactive surface coatings to prevent bacterial colonization. The results highlight the potential of catechol–thiol cross-linking as a versatile platform for engineering multifunctional glycoprotein hydrogels with applications in wound repair and antimicrobial surface engineering. Wet epithelial surfaces are coated in layers of mucus that hydrate, lubricate, and present a physicochemical barrier protecting the underlying tissue ( 1). Many of these critical biological functions are attributed to a family of glycosylated proteins called mucins, which assemble into viscoelastic, disulfide-linked networks ( 2) with bioactive properties ( 3, 4). The possibility of leveraging the mechanical and biochemical properties of mucins has motivated research on mucin-based biomedical materials ( 5– 7). However, applications such as wound dressings ( 8), antifouling and lubricious hydrogel coatings ( 9), and repair of depleted native mucus layers ( 10) require robust gelation and adhesion to tissue and implant materials in physiological environments, beyond the transient cross-linking ( 11) and adsorption ( 12) of native mucins. Enhanced cross-linking of mucin proteins has previously been achieved using disulfide bonding ( 13) or covalent modification ( 14, 15), and adhesion of mucin monolayers has been achieved by multistep covalent attachment to surfaces ( 16, 17), but there remains a need for strategies to simultaneously cross-link and adhere mucin-based hydrogels while preserving mucin bioactivity.