Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells(NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA)are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiationin vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficitsby enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, weadministered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampalneurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacitiesof treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nisslstaining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampaldentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3b/b-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreatedAPP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSCproliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3b/b-cateninpathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis,achieved by stimulating the Wnt/GSK-3b/b-catenin pathway. As such, PPD and OA arepromising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.