Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Valeton (Zingiberaceae) ( ) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrP ) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrP accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrP accumulation in the spleen of mice was also reduced. extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that extract could contribute to investigating the modulation of prion propagation.