Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/β‐catenin signal pathway confirmed by upregulated Wnt‐3a, phosphorylated glycogen synthase kinase‐3β (p‐GSK‐3β), and β‐catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin‐related protein 1 (p‐Drp 1). However, these effects of ICS II were blunted by XAV‐939, an inhibitor of Wnt/β‐catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/β‐catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.