Background: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofi-brillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (A beta) induced neural apoptosis. Moreover, overexpression of beta-secretase 1 (BACE1), A beta, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symp-toms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, pos-sesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily pene-trate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. Methods: The effect of artemether on memory protection and the associated molecular mechanisms were investi-gated in an A beta 25-35 induced cognitive impairments rat model. Results: Results of the in vivo study showed that oral administration of artemether significantly attenuated A beta 25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly down-regulated the endogenous expression of A beta, BACE1, mTOR, and Tau proteins in N2a cells. Conclusions: The beneficial effect of artemether against A beta 25-35-induced cognitive impairments was attributable to the downregulation of the expression of A beta, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.