A wide range of African plants (n = 20), used traditionally for the treatment and management of epilepsy, were selected and subjected to biological assays to assess their effectiveness in combating pentylenetetrazole (PTZ)-induced seizures in six days post fertilisation (dpf) zebrafish larvae. Ground plant material was extracted using solvents of varying polarity, six dpf larvae were incubated with the crude extracts for 18 hrs to determine the maximum tolerated concentration (MTC) for each plant extract. Of the 120 crude extracts tested, MTC values for 70 crude extracts were determined; the remaining 50 crude extracts were found to be highly toxic in the concentration range tested (10 -1000 µg/mL). For the bioactivity assay 70 crude extracts were tested for their effectiveness in reducing convulsions in PTZ-induced seizures in zebrafish larvae. Six crude extracts from Rauvolfia caffra Sond., Rauvolfia vomitoria Afzel, Withania somnifera (L.) Dunal., Annona senegalensis Pers. and Costus afer Ker. Gawl. were found to be active and marked as potential hits for further study. Rauvolfia caffra Sond. and Withania somnifera (L.) Dunal. extracts were found to be highly bioactive and were selected for further studies. Extracts of these two plants were fractionated to give 44 fractions, which were assayed for potential antiepileptic activity using the PTZ assay. Five fractions from Rauvolfia caffra Sond. reduced the locomotor activity of the larvae significantly, indicating their potential effectiveness as antiepileptic agents. From these five fractions, three compounds were isolated using preparative-HPLC. NMR structural elucidation of two of these compounds were identified firstly the known pleiocarpamine (1), as well as a previously unreported compound, to which we assigned the trivial name Rauverine H (2). Pleiocarpamine showed significant activity in reducing PTZ-induced seizures in zebrafish larvae at P < 0.05. The results of this study provide preliminary evidence to support the traditional use of Rauvolfia caffra Sond., in the treatment and management of epilepsy.