Astragalus mongholicus (AM) is a traditional medicinal herb used as a neuroprotective agent for its anxiolytic, antidepressant, antiamnestic, and antiaggresive effects. However, the mechanisms underlying its anti-convulsant properties are not well studied. In the present study, we examined the anticonvulsant effects on pentylenetetrazol (PTZ)-induced seizures in mice and the possible mechanisms of protection against oxidative damage and mitochondrial dysfunction in vitro. The behavioral studies showed that the root extract of AM had powerful anticonvulsant effects against seizures induced by PTZ and the biochemical studies showed that root extract of AM inhibited PTZ-induced increase in lipid peroxidation, protein oxidation and reactive oxygen species, and enhanced mitochondrial function. Electron spin resonance spectroscopy studies demonstrated that the extracts from the root and aerial parts of AM possess potent effects on scavenging hydroxyl and lipid free radicals. We found that AM extract significantly protected malondialdehyde-induced oxidative damage by ameliorating activities of the mitochondrial complexes I, II, malate dehydrogenase and mitochondrial membrane potential. These data suggest that the anti-convulsant effects of AM extract may be mediated by its protective actions against oxidative damage and amelioration of mitochondrial dysfunction.