Coptidis Rhizoma, a well known heat-clearing Chinese Materia Medica, exhibited multi-target anti-Alzheimer effectsin vitro through inhibition of AI342 aggregation, ACHE, and BACE1. Six berberine-like alkaloids were found to be the majoractive constituents of Coptidis Rhizoma by HPLC analysis along with activity assays. A standard combination of the six majoralkaloids was demonstrated to fully reproduce the in vitro effects of Coptidis Rhizoma. Molecular docking studies revealed thatberberine-like alkaloids could directly bind at the active sites of AI342, ACHE, and BACE1 through hydrophobic interactions,aromatic stacking, and electrostatic interactions.