This study aimed to prepare and characterize the orally disintegrating tablet (ODT) formulations containing the combination of levetiracetam (LEV) and carbamazepine (CBZ) (CBZ + LEV combination) for the treatment of epilepsy. The ODT formulations were prepared using the lyophilization (L) and direct compression (DC) methods. The flowability of the mixed powders used for DC formulation was evaluated. The quality control tests for the ODTs were performed. Also, the antiepileptic effects of pure drugs, their combination, and the suspension of CBZ + LEV-DC-ODT formulation were evaluated in the rats with pentylenetetrazole (PTZ)-induced epilepsy model. The obtained results for the mixed powders of the DC formulation (angle of repose: 26.18 ± 0.794°; compressibility index: 15.24 ± 0.764%) suggest that the flow properties of the powder blend were suitable for the preparation of CBZ + LEV-ODT using DC method. The mean values of diameter and hardness of L-ODTs and DC-ODTs were found to be 16.87 mm and 16.18 mm and 11.96 N and 30.11 N, respectively. The friability of both formulations was <1%. Both formulations were disintegrated in seconds. Drugs in L-ODT had faster dissolution than those in DC-ODT. Compared to the seizure scores obtained for the groups treated with LEV or CBZ, generally, there was a higher decrease in seizure scores in the groups treated with CBZ + LEV combination or the suspension of CBZ + LEV-DC-ODTs. Consequently, the ODT formulations containing the CBZ + LEV combination might be beneficial in the treatment of epilepsy.