Dehydroabietylamine derivatives have been reported to eliminate the superoxide anion (O2 c) and 1,1 dipheny-2-picrylhydrazyl radicals. In this work, several dehydroabietylamine derivatives were shown to have potent anti-oxidative activity in SH-SY5Y cells and exhibited significant inhibition of Ab42 selfmediated aggregation and the disaggregation of Ab42 aging fibrils. In particular, the compound 12N,18Nbis(caffeoyl)-14-nitrodehydroabietylamine (3b) showed the most potent inhibitory activity against Ab42 self-mediated aggregation with an IC50 value of 3.96 0.33 mM. Compound 3b decreased the production of Ab42 in swAPP HEK293 cells and showed neuroprotective activity against Ab42-induced cytotoxicity. Through reducing the production of the Ab42 species, compound 3b alleviated Ab42 induced paralysis in transgenic Caenorhabditis elegans strain CL4176. Considering its multifunctional activity and low cytotoxicity, 3b is considered to be a potential multifunctional agent for the treatment of Alzheimer's disease.