Osteoarthritis has been a major disease in recent years, which is mainly related to the breakdown of the lubri cation function of the cartilage sliding interface, along with the inflammation of the joint capsule. In this paper, one kind of novel biomimetic nanoparticles (NPs) lubricant, named CS-PS, is synthesized through chemically grafting hydrophilic sulfonic acid (SO3 − ) groups onto the surface of biocompatible and biodegradable chitosan (CS) NPs. Compared with control CS NPs, the as-synthesized CS-PS NPs exhibits excellent hydration and stability because of negatively charged surface zeta potential, along with extraordinary lubrication performance in water for realizing a super-low friction coefficient (COF) as ~0.01 at the sliding interface of PDMS elastomer-Ti6Al4V disk. Correspondingly, the CS-PS NPs can also be used as a drug carrier for aspirin, which presents very good drug loading and release behavior in PBS (pH = 7.4). MCS cells culture experiment proves that this kind of novel lubricant is nontoxic and biocompatible, for which may be expected to use as potential articular injective ma terial for the treatment of osteoarthritis.