Abstract: During biomedical treatments, friction between implanted or interventional medical materials and biological tissues is inevitable. Excessive friction and materials with poor biocompatibility may lead to tissue damage, inflammatory responses, wound infection, or even life-threatening consequences. Therefore, the development of materials with excellent lubricating properties and biocompatibility is of significant practical importance. Hydrogels have attracted widespread attention in the biomedical field due to their tunable physicochemical properties, customizable microstructures, biomimetic macroscopic design, and high water content. Because the structure and lubrication mechanisms of hydrogels resemble those of biological friction systems such as articular cartilage and tear films, hydrogels exhibit outstanding lubricity and biocompatibility in mimicking and replacing natural biological lubrication systems. First, the lubrication mechanism of hydrogels was elaborated, emphasizing the synergistic effect of elastic deformation for load distribution, fluid lubrication, boundary lubrication, and hydration lubrication. Furthermore, a detailed overview was presented of recent advances in hydrogel materials exhibiting high lubricity, including structured hydrogels with biomimetic fine macro- and micro-scale architectures, surface-lubricity-modified hydrogels inspired by the layered structure of natural cartilage, and bulk-lubricating hydrogels that emulated the high water content and sustained lubrication of biological tissues. Finally, the applications of biomimetic lubricating hydrogels in the biomedical field were summarized, such as articular cartilage repair and replacement, ocular treatments, tendon rupture repair, and coatings for interventional devices. Future perspectives were also provided to offer insights for ongoing and future research in this field.