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Oxidative stress is closely associated with the pathology of neurodegenerative diseases. The seeds of <i>Carthamus tinctorius</i> L. (CTS) and <i>Taraxacum coreanum</i> (TC) are reported as herbal medicines for neuroprotection. This study investigated the protective effect of CTS, TC, and their combination against oxidative stress induced by H₂O₂ in SH-SY5Y cells. The CTS and TC combination dose-dependently increased DPPH and ·OH radical scavenging activities compared with non-combination. The combination showed a higher increased cell survival rate in H₂O₂-stimulated SH-SY5Y cells than CTS or TC. Moreover, CTS, TC, and their combination-treated cells reduced LDH release and apoptotic cells. CTS, TC, and their combination also inhibited NO and ROS generation. Further, the combination of up-regulated antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and Bcl-2 protein expressions and down-regulated Bax expression. These findings suggest that the combination of CTS and TC may be beneficial to prevent and treat oxidative stress-mediated neurodegenerative diseases.