Oxidative stress plays a role in regulating a variety of physiological functions in living organisms and in the pathogenesis of articular cartilage diseases. Piper kadsura Ohwi is a traditional Chinese medicine that is used as a treatment for rheumatic pain, and the extracts have anti-inflammatory and antioxidant effects. However, there is still no study related to cell protection by P. kadsura. The P. kadsura extracts (PKE) were obtained by microwave-assisted extraction, liquid-liquid extraction, and column chromatography separation. The extracts could effectively scavenge free radicals in the antioxidant test, the EC50 of extracts is approximately the same as vitamin C. PKE decreased the apoptosis of SW1353 cells treated with H2O2 and could upregulate the gene expression of antioxidant enzymes (SOD-2, GPx, and CAT) and the Bcl-2/Bax ratio, as well as regulate PARP, thus conferring resistance to H2O2 attack. PKE protects cells against apoptosis caused by free radicals through the three pathways of JNK, MEK/ERK, and p38 by treatment with MAPK inhibitor. The identified components of PKE were bicyclo [2.2.1] heptan-2-ol-1,7,7-trimethyl-,(1S-endo)-, alpha-humulene, and hydroxychavicol by gas chromatography–mass spectrometry.