Osteoarthritis (OA), the most prevalent articular disease with the clinical syndrome of joint pain accompanied by varying degrees of functional limitation, reduces the quality of elderly life. In this study, the effects of Plebeian sage extract (PS) on anti-inflammatory and anti-articular cartilage degradation activities were evaluated in rats with surgically induced OA. PS supplement for 12 weeks significantly decreased Mankin scores, including inflammatory cell numbers, and improved surface cartilage damage and mean femur and tibia articular cartilage (AC) thicknesses in OA rats. PS diminished IL-1β, IL-6, TNF-α, MMP-2, MMP-3, and MMP-9, as well as lipocalin-2 levels in serum or cartilage, which were increased due to OA. The results suggested that PS decreased joint inflammation and loss of articular cartilage by suppressing provocative responses and synovial tissue decimation in the OA model. Thus, PS may be used as a novel potential therapeutic regime for OA in the elderly.