Objective Cerebral ischemia/reperfusion (I/R) is a potential factor for lethal injury, and currently lacks effective remedies. Bauhinia championii extracts (BCEs) have been reported to exhibit anti-oxidative and anti-hypoxia properties. The current work aimed to study whether BCE could alleviate neuronal injury caused by I/R. Methods To investigate the protective effects of BCE, oxygen-glucose deprivation/reperfusion (OGD/R) was applied to the HT22 cell line in vitro and to a cerebral I/R mouse model in vivo. Results Under OGD/R, the survival of HT22 cells was significantly prolonged after treatment with BCE. In vivo, BCE significantly reduced the infarct area and decreased neuronal apoptosis caused by I/R. It was further found that OGD/R could trigger endoplasmic reticulum (ER) stress and induce ER stress-mediated neuronal apoptosis in vivo and in vitro, while BCE could effectively alleviate ER stress and neuronal apoptosis. Conclusion These results suggested that BCE exhibits neuroprotective effects by reducing ER stress-mediated apoptosis after cerebral I/R injury. BCE may therefore be an effective therapeutic regimen against cerebral I/R damage.