Motivated by the aforementioned information and in continuation of our interest in developing multi-target inhibitors as potent candidates for the treatment of AD [27], we herein disclose the design, synthesis, and biological evaluation of a series of novel ligustrazine-based derivatives as multi-targeted inhibitors against AChE, BChE, and Aβ aggregation for potent treatment of AD. This evidence concerns the gene ACHE and Alzheimer disease.