Sleep disorder, migraine, cognitive and behavioral disorders, anxiety and depression are common comorbidities of epilepsy. The comorbidity rate of epilepsy patients is eight times that of the general population, which affects the prognosis and quality of life of epilepsy patients. Perampanel (PER), as a third-generation antiseizure medication, has shown promising clinical research and application in the treatment of comorbidities in epilepsy. PER can improve the total sleep time, sleep latency and sleep efficiency of patients with epilepsy comorbid sleep disorder. PER also shows good efficacy in reducing seizure and migraine attacks of patients with epilepsy comorbid migraine. Meanwhile, the impact of PER on overall cognitive characteristics is neutral, with no systematic cognitive deterioration or improvement, but behavioral changes are one of the most common adverse events related to PER. For patients with comorbid anxiety and depression, PER does not exacerbate the anxiety and depression of epilepsy patients, and the severity of anxiety and depression in some patients will improve. This article will review the mechanism of action and clinical treatment research progress of PER on comorbidities of epilepsy.