Objective Perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, has been approved as adjunctive therapy for focal and generalized epilepsy. Limited information is available regarding the measurable impact of anti-seizure medications (ASM). In this study, we aimed to investigate the effects of PER on electroencephalography (EEG) background activity and interictal epileptic discharge. Methods This study included all patients with a clinical diagnosis of epilepsy who underwent routine EEG before and after PER treatment between 2018 and 202EEG findings were examined according to their background activity and clinical features such as risk factors of epilepsy, the occurrence of sleep-related seizures, sleep disorders, intellectual disability, abnormality of magnetic resonance imaging and EEG, multifocal features on EEG, the duration between EEG and initiation of PER treatment, frequency of seizures before and after PER treatment (seizure freedom or >50% reduction in seizures), previous epilepsy surgery, the number of current and previous ASM, and dosage of PER. Results In a total of 11 patients, epilepsy type was focal in 8 (73%), all of the patients were on polytherapy, and 4 of them had undergone epilepsy surgery. PER treatment resulted in seizure freedom in 36% of patients and a >50% decrease in seizures in 55% of patients. There was no statistically significant relationship between background activity, phase reversal, and equipotential in EEG before and after PER treatment. In addition, pre- and posttreatment responses to activation procedures and disruption in sleep structure did not differ significantly. The relationship between seizure freedom and phase reversal decrease after PER treatment was statistically significant. The relationship between a >50% decrease in the frequency of seizures and epileptic discharges also reached statistical significance. Conclusion To summarize, seizure freedom following PER treatment appears to be associated with reduced epileptic discharge, and EEG monitoring might help determine prognosis.