The development of biomimetic lubricants with superior lubrication, anti-inflammatory activity, and biocompatibility is urgently needed for the treatment of osteoarthritis (OA). Inspired by the architecture of biological lubricin and the exceptional lubrication of synovial joints, we designed a proteinbased brush polymer by employing proteins as intrinsic macromolecular backbones. Specifically, we synthesized a biomimetic bottlebrush polymer, mHSA-g-PMPC, in which a denatured human serum albumin (HSA) backbone was grafted with zwitterionic poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC) brushes. The resulting drug-free biomaterial exhibits an ultralow coefficient of friction (μ < 0.01) and remains stable over 2000 friction cycles in aqueous and physiological media, primarily due tohydration lubrication of the PMPC side chains. In vitro evaluations confirmed that mHSA-g-PMPC exhibits high biocompatibility and significant anti-inflammatory properties. Overall, the biomimetic mHSA-g-PMPC bottlebrush polymer integrates well-defined molecular architecture with multifunctional biological performance, representing a promising drug-free strategy for potential OA treatment.