To provide multilayered combination therapies encompassing nanoparticles and organic peptides and to assess their efficacy in the treatment of arthritis.Fish oil protein (FP) was isolated from fish oil glands and tagged with spherical gold nanoparticles (GNPs). Tagged GNPs were encapsulated in DPPC liposomes (FP-GNP-DPPC) and characterized.FP increased the hydrophilicity of GNP, while encapsulation of FP-GNP within liposomes increased the hydrophobicity. In vitro release studies of FP-GNP-DPPC exhibited sustained release of FP in simulated synovial fluid. FP-GNP-DPPC injected into intra-articular joints of rats displayed anti-osteoarthritic effects in osteoarthritic rat model. This is the first study to report the anti-osteoarthritic activity of FP and DPPC encapsulated FP-GNP liposomes.