Objective: To investigate the effect and molecular mechanism of Nao Tan Qing (NTQ) on neural stem cell (NSC) proliferation in Alzheimer's disease (AD) mice. Methods: 5×FAD mice were randomly assigned to two groups, the AD group treated with ddH2O and AD+NTQ group orally administered with NTQ by gavage. Immunofluorescence staining, real-time quantitative PCR, and western blotting were used to evaluate neural stem cell proliferation in hippocampus. In vitro, neural stem cells were isolated and cultured with PBS, NTQ. Cell apoptosis and proliferation were assessed using the apoptosis and CCK-8 assays. Immunofluorescence staining was used to detect the number of SOX2+, BrdU+, and DCX+ cells. The mRNA and protein levels of Sox2 and Dcx were measured by real-time quantitative PCR and western blotting. The expression of key molecules CyclinD1, P27/Kip1 and Gata2 was detected by real-time fluorescence quantitative PCR and protein blotting; the expression level of Sox2 was detected by fluorescence quantitative PCR and protein blotting after the in vitro treatment of neural stem cells using CyclinD1-CDK inhibitor.Results: In the AD+NTQ group, the number of SOX2+ cells in brain significantly increased, with a marked elevation in Sox2 mRNA and protein levels compared with the AD group. In vitro, the diameter of neurospheres treatment with NTQ were significantly larged, along with the increased number of BrdU+, SOX2+, and DCX+ cells. Moreover, Sox2 and Dcx mRNA levels, as well as SOX2 protein level, were notably elevated. Mechanistically, the expression of GATA2 and its downstream molecule p27/Kip1 was decreased in the hippocampus of AD+NTQ mice, and the inhibitory effect on cyclinD1 was weakened in NSC proliferation. Addition of CyclinD1-CDK inhibitor attenuated the increase in Sox2, Dcx expression triggered by NTQ. Conclusion: NTQ maintains neural stem cell proliferation and alleviates cognitive deficits in AD mice by modulating the GATA2-p27/Kip1-cyclinD1 signaling pathway.