Amyloid aggregation and deposition are associated with many intractable human diseases. Although the inhibition of amyloid protein aggregation has been well-studied, the disaggregation and dissolution of existing amyloid fibrils is less known. Taking a fibrillar assembly of amyloid beta (A beta) peptide as the model system, here we report multivalent polymer-peptide conjugates (mPPCs) that disassemble preformed A beta fibrils into dispersible sub 100 run structures. Atomic force microscopy and dynamic light scattering studies show that the disassembly rate of preformed A beta fibrils is controlled by the molecular weight of mPPCs. Rate equations on fibril disappearance are deduced from a simple model, which indicate that the disassembly reaction is first-order in the concentration of A beta fibrils and a pseudo-first-order reaction in the concentration of peptide moieties on mPPCs, respectively. We eliminate the possibility that the disassembly occurs by the association between mPPCs and A beta monomer/oligomers based on circular dichroism and Thioflavin T fluorescence assays. It is mostly likely that the mPPCs disassemble A beta f(i)brils through a direct interaction. The mPPCs may thus offer a general macromolecular design concept that breaks down existing amyloid fibrils in a predictable fashion.