Background Epilepsy is characterized by acute recurrent seizures. The control of seizures is largely hampered by the tolerance to current anti-seizure drugs. Complementary anti-convulsant pharmacotherapies are urgently needed. Objective Here, we aimed to investigate the anti-convulsant effects of Xingnaojing Injection (XNJ) which is an approved Traditional Chinese Medicine injection on different acute seizure models in mice. Methods The effects of XNJ were tested on the maximal electroshock (MES), pentylenetetrazol (PTZ) and kainic acid (KA) acute seizure models. Also, whether XNJ can directly inhibit hippocampal neuronal firings were examined by in vitro electrophysiology. Results XNJ could shorten the durations of generalized tonic-clonic seizures in the MES model. It also significantly prolonged the latencies to generalized myo-clonic seizures in the PTZ model. In the KA model, XNJ showed various efficacies including inhibiting the seizure stages, prolonging the latency to the occurrence of the first seizures or generalized seizures, shortening the seizure durations, decreasing the numbers of generalized seizures. In vitro electrophysiological recordings further verified XNJ directly inhibited both the spontaneous and evoked action potentials of hippocampal pyramidal neurons, but did not influence the excitatory or inhibitory synaptic transmissions. Conclusion These findings proposed XNJ as an alternative anti-convulsant pharmacotherapy for controlling acute epileptic seizures.