Beta-amyloid (A beta) oligomers are strongly associated with the cascade of harmful events leading to neurodegeneration in Alzheimer's disease (AD). Elimination of A beta oligomers or inhibition of A beta assembly is a valuable therapeutic approach for the treatment of AD. Here, we obtained a mimotope of A beta oligomers, AOEP2, by screening a peptide library using oligomer-specific antibodies. The antibodies induced by AOEP2 specifically recognize A beta oligomers rather than monomers and fibrils. Interestingly, the AOEP2 peptide binds to A beta monomers and inhibits the formation of A beta oligomers and beta-sheet structure, reduces A beta 42-induced neurotoxicity, and decreases the release of proinflammatory cytokines. Taken together, AOEP2, a novel multifunctional peptide directly or indirectly targeting A beta, has promising therapeutic potential for AD.