Abstract Aims This study investigates the effect of a new combination of glucosamine hydrochloride, chondroitin sulfate, methylsulfonylmethane, Harpagophytum procumbens root extract (standardized to 3% harpagoside) and bromelain extract (GCMHB) on formalin-induced damage to cartilage tissue in the rat knee joint and evaluates this combination in comparison with another combination of glucosamine hydrochloride, chondroitin sulfate and methylsulfonylmethane (GKM). Materials and methods Animals in the control group were injected with formalin into the knee joint (FCG). Animals in the GCMHB-500 group were given 500 mg/kg GCMHB + formalin, and those in the GKM-500 group were given 500 mg/kg GKM + formalin. Finally, a healthy group (HG) was also used. GCMHB and GKM were administered to rats orally once a day for 30 days. At the end of this period, the rats were sacrificed and the levels of MDA, NO, 8-OH/Gua, and tGSH in the knee joint tissue were measured. Analysis of IL-1β and TNF-α gene expression was done and the tissue was evaluated histopathologically. Key findings MDA, NO and 8-OH/Gua levels and IL-1β and TNF-α gene expression were significantly lower in the GCMHB-500 group compared to the FCG group, whereas tGSH was significantly higher in the GCMHB-500 group than in the FCG group. No significant difference was found for the IL-1β, TNF-α and oxidant/antioxidant parameters between the GKM and FCG groups. The histopathological analysis showed that GCMHB could prevent damage to the cartilage joint, whereas GKM could not. Significance GCMHB may be used clinically by comparing with GKM in the treatment of osteoarthritis.