BACKGROUNDS/OBJECTIVES: This study examined the anti-osteoarthritic effects of a Linn ethanol extract (CLE), standardized to 500 mg/g of curcuminoids, in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) Sprague-Dawley (SD) rats. MATERIALS/METHODS: The rats were divided into a normal control group (NC), OA control group (OC), OA +10, 20, 30, or 50 mg/kg body weight (BW)/day CLE-administered group (O+CL10, O+CL20, O+CL30, or O+CL50), and OA+150 mg/kg BW/day methyl sulfonyl methane (MSM, positive control)-administered group (O+M). The rats were given oral doses of CLE or MSM for 5 weeks, with an intra-articular injection of MIA into their knee joints on the 15th day to induce OA. Micro-computed tomography, histological examination, and immunofluorescence staining were performed on the knee joint. The inflammatory mediators, cytokines, and matrix metalloproteinase (MMP) mRNA expression were measured in the knee joint synovial fluid. RESULTS: The OC group showed more severe knee joint swelling and subchondral bone erosion than the NC group, and aggrecan and type II collagen expression in the articular cartilage was reduced. The OC group exhibited lower mRNA expression of inflammatory mediators, cytokines, and MMPs than the NC group. In OA-induced rats, the oral administration of the CLE reduced knee swelling and cartilage degradation and increased aggrecan and type II collagen expression in the articular cartilage. CLE administration reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, MMP-2, MMP-3, MMP-9, and MMP-13 in the synovia of knee joints. In particular, these levels reached the same as the positive control group, the O+M group. CONCLUSION: The CLE had potent anti-OA effects in MIA-induced OA rats by suppressing the expression of inflammatory mediators, cytokines, and MMPs, alleviating cartilage degradation. Hence, the CLE is a potential functional food ingredient that can prevent and improve OA.