The acid-base balance of the brain is critical to the functioning of the nervous system. The mechanisms that maintain acid-base homeostasis in the brain are complex and regulated by a variety of transporter proteins and enzymes. Slight changes in acid-base balance can affect neuronal excitability and even lead to epilepsy. Epilepsy is a common neurological disease with complex pathogenesis and numerous causes. Drug therapy is still the main method, but the treatment effect is limited. Therefore, it is urgent to clarify the pathological mechanism of epilepsy and explore new treatment directions This study provides an overview of the transporter proteins (acid-sensing ion channel, Na+/H+ exchanger, Na+/HCO3- cotransporters, anion exchangers, carbonic anhydrases) and the regulation of acid-base balance in the lungs. This study also introduces how these transporters participate in the stable maintenance of brain acid-base balance and their influence in epileptogenesis from both basic and clinical aspects in detail, providing new targets for epilepsy treatment and intervention.