Pergularia daemia Forsk. (Choiv.) (Asclepiadaceae) is widely used in Cameroonian’s folk medicine to treat epilepsy and infantile convulsions. In the present study, anticonvulsant effects of Pergularia daemia aqueous extract and possible antioxidant mechanisms were investigated on pentylenetetrazole (PTZ)-induced kindling model of epilepsy. All groups, excluding control group were kindled by 11 injections (i.e. 22 days) of PTZ (35 mg/kg, i.p.), one time every alternate day (48 ± 2 h), until the development of kindling (i.e. the manifestation of stage 5 of seizures for two successive trials in control animals). On the 26th day (i.e. the 12th injection), all mice were challenged with PTZ (75 mg/kg, i.p.). Following the completion of behavioral studies, hippocampi were removed and oxidative stress parameters were determined. P. daemia extract (24.5-49 mg/kg) significantly protected mice against myoclonic jerks and clonic seizures. The extract (12.3-49 mg/kg) significantly decreased the number of myoclonic jerks and development of PTZ kindling. PTZ-kindling induced significant oxidative stress alterations that were reversed by the extract. These results suggest that P. daemia has anticonvulsant effects facilitated in part by antioxidant activities. This clarifies consequently, its use in traditional medicine to treat epilepsy in Cameroon.