While soluble forms of amyloid-β (Aβ) and Tau work together to drive healthy neurons into a disease state, how their interaction may control the prion-like propagation and neurotoxicity of Tau is not fully understood. The cross-linking via disulfide bond formation is crucial for Tau oligomers to obtain stable conformers and spread between cells. This work thus focuses on how Aβ regulates this critical process. By studying the interactions between Aβ and Tau, a construct that mimics the Tau R3 isoform, has a similar length to Aβ42, and contains one cysteine (Cys-322), we discovered that fresh Aβ could protect Tau against the formation of disulfide cross-linked dimers. We showed that the monomeric and small Aβ oligomers (the "nonamyloidogenic Aβ") efficiently disassembled tau dimers and heparin-induced Tau oligomers to recover Tau monomers. Interestingly, Aβ serves the role of an antioxidant to prevent disulfide bond formation, as supported by the experiments of Aβ with cystine. Furthermore, using cyclosporine A (CycA), a macrocyclic β-sheet disruptor, we demonstrated that targeting amyloidogenic Aβ with CycA does not affect the Tau disassembly driven by Aβ. Separately, we assessed the initial toxicity of Aβ and Tau in acute brain slices and found that Aβ is more toxic than Tau or the two peptides combined. Our work highlights a potential protective role of Aβ monomers in AD that was previously overlooked while focusing on the mechanism behind Aβ aggregation leading to tau dysfunction.