The present invention discloses a chrysotoxine bibenzyl derivative shown as a formula I. R1 represents C=O, CH2, NH, S=O or a covalent bond; R2 represents alkyl, phenyl, substituted phenyl, benzene ring substituted C1-3 alkyl, C5-C6 cycloalkyl, and a pentabasic or hexahydric unsaturated heterocyclic group containing one or more O, S and N. The invention also discloses a simple and efficient preparation method of the chrysotoxine bibenzyl derivative, and application of the derivative to the preparation of neuroprotective drugs and drugs for treating Alzheimer disease. The chrysotoxine 4-O-substituted bibenzyl derivative has significant protective effect on A beta-induced neuronal apoptosis, and is a potential novel chemical entity for the treatment of AD.