Neurologic disorder epilepsy, characterized by recurring convulsions, challenges healthcare personnel and patients. Many antiepileptic medicines (AEDs) have helped cure seizures, but the oral route can be problematic, especially for patients who have problems swallowing or complying. Antiepileptic suppositories show promise as a treatment option after investigating other administration routes. Phenobarbital, a popular antiepileptic, has managed seizures for decades. Phenobarbital in suppository form could revolutionize medicine delivery and overcome traditional administration challenges. This dissertation investigates antiepileptic suppositories' complicated pharmacology and therapeutic potential, focused on phenobarbital. This study reviews relevant scholarly works, clinical trials, and pharmaceutical technology to determine the pros, cons, and potential future developments of phenobarbital-loaded suppositories for epilepsy. The following chapters will explain pharmacokinetics, patient-centered benefits, and potential drawbacks of antiepileptic suppositories. This dissertation aims to advance novel antiepileptic delivery strategies by carefully analyzing the evidence and understanding phenobarbital's unique pharmacological properties. It intends to advance epilepsy treatment paradigms.