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Osteoarthritis, the most common joint disease worldwide, is a degenerative disease characterized by cartilage degeneration and inflammation. The active ingredients in the traditional Chinese medicinal plant Achyranthes bidentate can be used to treat waist, leg, and joint pain caused by rheumatism arthralgia. In this study, we identified the optimal microwave extraction protocol for saponins from A. bidentate, evaluated their protective effects against IL-1β-induced inflammation in SW1353 human chondrocytes, and explored their protective pathway. The microwave-extraction parameters required to obtain the maximum yield of A. bidentate saponins using 80% ethanol were identified using response surface methodology. The parameters were solid-liquid ratio, 1:10; extraction time, 20 min; power, 721 W; temperature, 65 °C. The actual yield of saponins extracted was to be 194.01 μg/mg extract. The SW1353 cells were pretreated with A. bidentate extract (ABE) at a concentration of 50 or 100 μg/mL for 3 h, after which an inflammatory response was stimulated using IL-1β. The ABE significantly reduced the expression of proinflammatory factors IL-6, TNF-α, COX-2, iNOS, PGE2, and NO, and inhibited NF-κB activity, effectively attenuating the inflammatory response. ABE also inhibited MMP13 and ADAMTS-5 expression, reducing IL-1β-induced degradation of the extrachondral matrix. This confirmed that ABE effectively inhibits NF-κB activity and reduces IL-1β-induced inflammation, extracellular matrix degradation, and expression of apoptotic proteins Bax and caspase-3. Therefore, ABE has potential as a new botanical drug for preventing osteoarthritis.