Because the deposition of β-amyloid protein (Aβ) is a consistent pathological hallmark of Alzheimer's disease (AD) brains, inhibition of Aβ generation, prevention of Aβ fibril formation, or destabilization of preformed Aβ fibrils would be attractive therapeutic strategies for the treatment of AD. We examined the effects of several medicinal herbs used in traditional Chinese medical formulae on the formation and destabilization of Aβ fibrils by using the thioflavin T binding assay, atomic force microscopic imaging, and electrophoresis. Our study demonstrates that several of these herbs have potent inhibitory effects on fibril formation of both Aβ1–40 and Aβ1–42 in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited Aβ aggregation most intensively. Significant destabilization of preformed Aβ1–40 and Aβ1–42 fibrils was also induced by Uncaria rhynchophylla as well as some other herb extracts. Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective. Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Aβ fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD. © 2006 Wiley-Liss, Inc.