Ameliorating effects of methanol extracts of Basidiomycetes against in vitro and in vivo model of Alzheimer's disease were investigated. The extracts of Cordyceps ophioglossoides and Hypocrea citrina var. citrina prevented the beta-amyloid((25-35)) (Abeta((25-35)))-induced cell death in SK-N-SH neuronal cells. However, in rat model of Alzheimer's disease, 30-d intraperitoneal administration with only the extract of Cordyceps ophioglossoides significantly prevented spatial memory loss by intracranial injection of Abeta((25-35)), which was assessed in water maze task. Interestingly, the scavenging activity of the reactive oxygen species (ROS) generated in Abeta((25-35))-treated cells was also found in the extract of Cordyceps ophioglossoides, but not in the extract of Hypocrea citrina var. citrina. These results suggest that the extract of Cordyceps ophioglossoides may protect the Abeta-induced neuronal cell death and memory loss through free radical scavenging activity. These results further suggest that Cordyceps ophioglossoides mycelium may be valuable for the protection from Alzheimer's dementia.