Alzheimer´s disease (AD) is a progressive neurodegenerative disease and is the most common form of dementia in the elderly. The lack of disease-modifying therapeutics for AD has imposed a huge social burden. The pathological hallmarks of AD include formation of amyloid-β (Aβ) plague in extracellular space and aggregation of Tau protein within neurons. Both Aβ- and Tau-elicited neurotoxicity could significantly contribute to the onset and progression of AD. Accumulated evidence has suggested that enhanced autophagic clearance of Aβ and Tau could significantly slow down the progression of neurodegeneration in AD. We thus seek to identify novel autophgy-enhancing agents from herbal extracts and determine whether herbal extracts effective on inducing autophagy can reduce Aβ-elicited neurotoxicity. A cell-based reporter assay for autophagy is established to perform the primary screen of herbal extracts. Effective herbal extracts are validated by a secondary cell-based autophagy assay independently. The in vivo efficacy of herbal extract is subsequently determined by using an Aβ42-injection mouse model of AD. We have now identified an herbal extract (HE238) that exhibit potent biological efficacy in suppressing the neurotoxicity elicited by amyloidopathy. Our data show that treatments with HE238 can effectively induce autophagy to promote the clearance of Aβ in cultured cells. Oral administration of HE238 for 2 month also significantly improves the cognitive function in an Aβ42-injection mouse model. Together, our data suggest that the active ingredients of HE238 could present an enormous resource for AD-alleviating agents.