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A 19-year-old White Brazilian female with epilepsy was evaluated after failing to become seizure free even with the use of antiepileptic drugs. Due to difficulty of communication, a neurocognitive assessment indicated the presence of attenuated delayed psychomotor and cognitive development. In addition to refractory epilepsy, with 30 seizures/day, a clinical diagnosis of lissencephaly was confirmed after MRI and electroencephalography monitoring. The intervention for reducing the seizures consisted of vagus nerve stimulation (VNS). After 30 days, relatives reported significant cognitive and behavioral improvement, such as reduced aggression and impulsivity, which lasted 60 and 90 days (follow-up). Furthermore, there was an improvement in psychomotor and self-care capacity. At this time, there was a significant reduction in seizures from about 30 seizures/month to 5 seizures/month. This case highlights the significant cognitive improvement even before the reduction of seizures in a patient with intractable drug-resistant epilepsy after VNS implant. Even though this is a rare case, the use of VNS in lissencephaly may be a potential tool for cognitive and behavioral improvement.