Background: Astragalus and Panax notoginseng are traditional Chinese Medicines used for the treatments of ischemic cerebrovascular disease, being often combined together in China and achieving a good effect. Objective: The objective of this study is to investigate the effects of astragaloside-IV (AST-IV) (the effective component of Astragalus) combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 (the effective components of P. notoginseng) on oxidative stress injury after cerebral ischemia-reperfusion in mice, and to explore the mechanisms through nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Materials and Methods: C57BL/6 mice were randomly grouped after treated for 3 days, the model of cerebral ischemia-reperfusion injury was established, and the brain tissues were detected. Results: AST-IV combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 could increase significantly the survival rate of nerve cell; decrease the contents of malondialdehyde, nitric oxide, increase the activity of superoxide dismutase and the level of glutathione; Nrf2 was down-regulated in the cytoplasm while up-regulated in nucleus, nuclear translocation rate raised as well as HO-1 messenger ribonucleic acid and protein expressions increased. The effects of four active components combination were better than those of the active components alone. Conclusion: Active components of Astragalus and P. notoginseng had the effects against cerebral ischemia-reperfusion injury, which were related to the antioxidative stress after cerebral ischemia-reperfusion. AST-IV combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 could strengthen the antagonism effects on ischemia-reperfusion and oxidative stress injury, the mechanism underlying might be associated with jointly activating Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion.