The plant Synedrella nodiflora (L) Gaertn is traditionally used by some Ghanaian communities to treat epilepsy. To determine if this use has merit, we studied the anticonvulsant and other neuropharmacological effects of a hydro-ethanolic extract of the whole plant using murine models. The anticonvulsant effect of the extract (10–1000 mg/kg) was tested on the pentylenetetrazole-, picrotoxin-, and pilocarpine-induced seizure models and PTZ-kindling in mice/rats. The effect of the extract was also tested in the formalin-induced pain, acetic acid-induced writhing assay, ethopharmacological paradigms, in vitro antioxidant properties. The extract showed potent effect in all the experimental models of seizures employed, antinociceptive, antioxidant, motor incoordination and sedative effects. In summary, the hydro-ethanolic extract of the whole plant of S. nodiflora possesses anticonvulsant effects, possibly through an interaction with GABAergic transmission and antioxidant mechanisms and muscle relaxant effects. These findings thus provide scientific evidence in support of the traditional use of the plant in the management of epilepsy.