Purpose: Horse is a relevant animal model to study osteoarthritis (OA) in human, the main cause of morbidity in developed countries. Human and horse patients both suffer from OA, and no treatment allowing cartilage regeneration currently exists. Among the emerging therapeutic strategies, nanomedicines could efficiently and sustainably deliver drugs in joints. The aim of this project is to develop functionalized nanogels that could improve mechanical functions and protect the cartilage against inflammation and degradation processes. Therefore, two polysaccharidic nanohydrogels (NGs) functionalized with peptides, either an antagonist of endothelin (B) or bradykinin (R) receptors were studied. Methods and Materials: Equine articular chondrocytes (eACs) cultured as monolayers were incubated with functionalized NGs, alone or combined, to test their biocompatibilities. Secondly, equine cartilage 3D organoids were used to determine the effect of NGs at cellular (eACs phenotype) and tissue levels (eACs environment). To mimic the OA inflammatory context, experiments were performed in the presence of IL-1. Results: NGs had no cytotoxic effect, did not alter the eACs viability/proliferation. The combination of both NGs (B+R) decreased the mRNA levels of markers of cartilage extracellular matrix degradation Mmp1, 3, and of inflammation IL-6, -18 and Inos in the organoid model. The nitric oxide (inflammatory mediator) levels and the eACs SA-βgal activity were also downregulated by NGs treatments. Considering matrix components, low expression of type II collagen has been observed at the protein level while that of type I collagen was decreased. Additionally, the NGs (B+R) restricted the downregulation of mRNA levels of hyaline cartilage markers and the upregulation of inflammatory and catabolic markers induced by IL-1. Conclusion: Further in vivo studies in horses are required to confirm the in vitro data. Nevertheless, our results strongly suggest that NGs (B+R) could protect cartilage from inflammation and degradation. These NGs could evolve with the addition of a pro-anabolic factor to improve cartilage regeneration.