Abstract This study investigated the neuroprotective effects of cyanidin-3- O-β- d-glucopyranoside (C3G) from the mulberry fruits on neuronal cell damage. A 1% HCl–MeOH mulberry fruit extract was shown to have a cytoprotective effect on PC12 cells that had been exposed to hydrogen peroxide. The extract inhibited the cerebral ischemic damage caused by oxygen glucose deprivation (OGD) in PC12 cells. The neuroprotective effect of the mulberry fruit extract was further demonstrated in vivo using a mouse-brain-injury model with a transient middle cerebral artery occlusion (MCAO). C3G was isolated as a neuroprotective constituent from the mulberry fruit extract. Compared with the control group, C3G had neuroprotective effects on the PC12 cells exposed to hydrogen peroxide in vitro and on cerebral ischemic damage in vivo.