Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of a water soluble artemisia annua extract (Ex1) on AD. Oral administration of Ex1 to AD 3xTg mice significantly improved the cognitive deficits, reduced Aβ accumulation, hyper-tau-phosphorylation and the release of inflammatory factors and apoptosis. Moreover, Ex1 promoted the survival and proliferation of neural progenitor cells (NPs), increased the expression of synaptic proteins and neuronal cell survival. Further assessment of the mechanisms implicated revealed that Ex1 regulates YAP signaling pathway in 3xTg AD mice. Similarily, Ex1 significantly reversed Aβ1-42-induced increase of ROS levels, caspase-3 activity, neuronal cell apoptosis, inflammation, and the phosphorylation of Tau in vitro. In addition, Ex1 also regulated YAP signaling in PC12 cells in a time and concentration-dependent manner further validating the involvement of this pathway. Consistent with this hypothesis, either inhibition of YAP signaling pathway using a specific inhibitor or CRISPR cas9 knockout of YAP gene in PC12 cells reduced the neuroprotective effect of the Ex1.Taken together, our findings suggest that Ex1 may be a new multi-target anti-AD drug that can be used in the prevention and treatment of Alzheimer’s disease.