Abelmoschus esculentus L. has favorable nutritional/medicinal features. We found the content of total flavonoids in flower extract to be the highest (788.56 mg/g) of all the different parts of A. esculentus; according to high-performance liquid chromatography, the quercetin-3-O-[β-D-glu-(1 → 6)]-β-D-glucopyranoside content was 122.13 mg/g. Protective effects of an extract of the total flavonoids of A. esculentus flowers (AFF) on transient cerebral ischemia-reperfusion injury (TCI-RI) were investigated. Compared with the model group, mice treated with AFF (300 mg/kg) for 7 days showed significantly reduced neurologic deficits, infarct area, and histologic changes in brain tissue, accompanied by increased contents of superoxide dismutase, whereas contents of nitric oxide and malondialdehyde decreased. AFF upregulated the expression of Nrf2, HO-1, and NQO1. These data suggest that AFF protects against TCI-RI by scavenging free radicals and activating the Nrf2-ARE pathway.