The present study investigated the neuroprotective effect of anthocyanidins, including cyanidin, delphinidin, malvidin, pelargonidin, and peonidin, against hypoxia in C6 glial cells. The cells were first incubated with a medium containing anthocynidin in normoxia condition and then with a medium containing sodium dithionite (Na2S2O4) in an anaerobic incubator for the hypoxia treatment. Methylthiazole tetrazolium test and evaluation of antioxidant enzyme activities and glutathione concentration were performed on the treated cells. At least 74% of the C6 cells preincubated with 25 mg/L of any of the five anthocyanidins in serum-free Dulbecco's modified Eagle's medium at 37 °C for 24 h survived the hypoxia treatment as compared with a survival rate between 47 and 59% for the control that was preincubated without an anthocyanidin. The cells preincubated with any of the five anthocyanidins showed higher catalase activity and glutathione concentration after the hypoxia treatment as compared with the corresponding samples without the preincubation with anthocyanidin. The cells preincubated with malvidin, pelargonidin, or peonidin also showed higher superoxide dismutase activities. The results of this study justify further research for the development of anthocyanidins into neuroprotective food ingredients against hypoxia injury.