Inhibition of the accumulation of amyloid β-peptide (Aβ) and the formation of β-amyloid fibrils (fAβ) from Aβ, as well as the destabilization of preformed fAβ in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAβ formation from Aβ(1–40) and Aβ(1–42) and destabilize preformed fAβ(1–40) and fAβ(1–42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and destabilization of fAβ(1–40) and fAβ(1–42) at pH 7.5 at 37°C in vitro. We next compared the anti-amyloidogenic activities of Cur and RA with NDGA. Cur and RA dose-dependently inhibited fAβ formation from Aβ(1–40) and Aβ(1–42), as well as their extension. In addition, they dose-dependently destabilized preformed fAβs. The overall activities of Cur, RA, and NDGA were similar. The effective concentrations (EC50) of Cur, RA, and NDGA for the formation, extension, and destabilization of fAβs were in the order of 0.1–1 μM. Although the mechanism by which Cur and RA inhibit fAβ formation from Aβ and destabilize preformed fAβ in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD. © 2004 Wiley-Liss, Inc.