<p>Osteoarthritis (OA) is a common degenerative joint disease. Insufficient joint lubrication in OA patients leads to joint pain, stiffness, and restricted normal physiological activity; therefore, restoring joint lubrication is a key strategy for OA treatment. This review summarizes recent advances in single-function and multifunctional lubricants from three aspects: structure, function, and research methodologies. Single-function lubricants primarily rely on hydration lubrication mechanisms to reduce the coefficient of friction and achieve joint lubrication and wear reduction. However, because they focus solely on interfacial lubrication performance and exhibit limited functionality, they are insufficient to halt the complex pathological progression of OA. This limitation has driven the emergence of multifunctional lubricant systems incorporating anti-inflammatory, antioxidant, tissue repair, and regenerative functions, as well as intelligent stimulus-responsive capabilities. In addition, this review highlights the synergistic roles of multiscale interfacial characterization techniques and molecular dynamics simulations in elucidating both biological and biomimetic lubrication mechanisms. The emerging applications of artificial intelligence and machine learning in lubrication performance prediction, inverse molecular design, and multiscale data integration are also discussed. Finally, key translational barriers are analyzed, including the heavy reliance on idealized model systems and the lack of standardized evaluation criteria. This review aims to provide a scientific foundation and new perspectives for the development of biomimetic joint lubricants and the clinical treatment of osteoarthritis.</p>