Currently, prolong use of standard anti-epileptics may cause tolerance and ineffective for about 30% of epileptic patients. Medicinal plants provide an attractive therapeutic effect in preventing and treating seizures in traditional and folk medicine. In this study, we investigate the antiepileptic effects of PTAT decoction on acute and chronic seizure models in mice and explore the potential mechanisms. PTAT decoction dose-dependently protected mice against MES and PTZ induced seizure. Meanwhile, it decreased the seizure severity and reduced seizure-caused anxious behavior in the PTZ-kindling mice, suggesting a significant antiepileptic activity and anxiolytic/anxiogenic potential. PTAT decoction dose-dependently increased the levels of GSH and the activity SOD and CAT, while decreased the level of MDA in the hippocampi of treated mice. Furthermore, a significant decrease in the proinflammatory cytokine levels, including TNF-α, IL-1β, IL-6 and MCP-1 was found in treated mice compared with the mice in the vehicle + PTZ group. Moreover, PTAT decoction dose-dependently reversed the alterations induced by PTZ in GABA, GABA-T, L-GAD and glutamate levels in kindling mice, showing an effect on the modulation of the GABA neurotransmission. Thus, PTAT decoction has a promising anticonvulsant activity mediated via multiple mechanisms, which might be used as an up-and-coming phytotherapy strategy in the management of epilepsy and its complications.