Oxidative stress is implicated in brain damage associated with ischemia-reperfusion. Natural antioxidants found in some plants used in folk medicine have been indicated as potential neuroprotective agents. Here we investigated whether Trichilia catigua, a traditional Brazilian herbal medicine alleged to exhibit a variety of neuropharmacological properties (antidepressant, anti-neurasthenic, anti-inflammatory etc.), could have neuroprotective properties in rat hippocampal slices subjected to 2 h oxygen and glucose deprivation (OGD) followed by 1 h reperfusion. Ischemia-reperfusion (I/R) significantly decreased mitochondrial viability, increased dichlorofluorescein oxidation above control both in the incubation medium and slices homogenates, increased lactate dehydrogenase into the incubation medium and decreased non-protein thiols. T. catigua (40-100 μg/mL) protected slices from the deleterious effects of OGD when present before OGD and during the reperfusion periods. Oxidative stress in the medium was also determined under different conditions and the results demonstrated that T. catigua could not protect slices from I/R when it was added to the medium after ischemic insult. Although the translation to a real in vivo situation of I/R is difficult to be done, the results indicated that T. catigua should be used as preventive and not as a curative agent against brain damage.