This study aimed to investigate the neuroprotective effects of breviscapine (Bre) against ischemic stroke and its underlying mechanisms using a middle cerebral artery occlusion/reperfusion rat model. Rats were randomized into three groups: Bre group, NaCl control group, and sham-operated (Sham) group. Following Bre treatment, a range of neurobehavioural tests were conducted, and the infarct volume was measured using TTC staining. Histopathological changes in the cerebral cortex were observed using Nissen staining, while proliferation and differentiation of neural stem cells were examined using immunofluorescence. Finally, the protein expression level of the Wnt3a/beta-catenin/transcription factor 4 (Wnt3a/β-catenin/TCF4) signaling pathway was detected by immunoblotting. The results showed that compared with the NaCl group, Bre treatment administration significantly accelerated body weight recovery, improved neurological function scores, enhanced motor coordination, reduced cerebral infarct volume, and attenuated neuronal damage in the per-infarct cortex. Analysis of immunofluorescence experiments showed that, Bre treatment increased the number of neuroepithelial stem cell protein (Nestin) and antigen Ki-67/doublecortin (Ki67/DCX)-positive cells in the subventricular zone, promoted the proliferation and differentiation of endogenous neural stem cells (eNSCs), Western blot experiments analysis revealed upregulated protein expression of Wnt3a, β-catenin, hosphorylated glycogen synthase kinase-3β (p-GSK-3β), TCF4, Cyclin D1, and neurogenin 1(Ngn1) in Bre-treated rats, demonstrating activation of the Wnt3a/β-catenin/TCF4 signaling axis. The results suggest that Bre may promote the proliferation and differentiation of eNSCs by activating the Wnt3a/β-catenin/TCF4 pathway, and then repair the neurological function after ischemic stroke.