As an essential component of wearable technology, skin adhesion plays a critical role in a wide range of wearable device applications. To maintain effectiveness and safety in daily use, skin adhesives must exhibit strong wet adhesion and high biocompatibility, particularly for devices that remain in contact with the skin for extended periods under humid and dynamic conditions. A comprehensive understanding of skin adhesion’s chemical mechanisms is fundamental to advancing this technology. Nature offers valuable inspiration, as numerous organisms have evolved sophisticated chemical and physical adhesion strategies that enable strong and reversible bonding. This review begins by exploring the historical development of nature-inspired skin adhesives, followed by a detailed examination of their performance in moist environments. Particular emphasis is placed on the covalent and non-covalent interactions between adhesive materials and skin surface functional groups, considering both biocompatibility and wet adhesion properties. Additionally, we discuss strategies to mitigate hydration-related challenges alongside an overview of characterization techniques, including mechanical, chemical, and biological testing methods. The classification of nature-inspired skin adhesives into chemical and physical approaches is presented, highlighting their applications in thermal management, energy harvesting, wound care, and transdermal drug delivery. Finally, we identify current limitations and propose design strategies to guide the development of next-generation skin adhesives, providing a clear trajectory for future research.