BACKGROUND: Landau-Kleffner Syndrome (LKS) and Autism Spectrum Disorder (ASD), both neurodevelopmental disorders, are frequently associated with epileptic seizures and characteristic epileptiform activity. Electrical Status Epilepticus during Sleep (ESES) is commonly observed in LKS, while Interictal Epileptiform Discharges (IEDs) are typical in ASD. Adrenocorticotropic hormone (ACTH) treatment has demonstrated the potential to reduce the indexes of these related discharges and the number of seizures. OBJECTIVE: This retrospective study aimed to assess the response to ACTH treatment in children diagnosed with LKS or ASD, both with and without epileptic seizures. METHODS: The study included 236 children, with separate analyses performed for those diagnosed with LKS or ASD. EEG recordings and treatment outcomes were retrospectively evaluated. Key assessments included changes in the indexes of ESES and IED, seizure control rates, and reported side effects. RESULTS: ACTH treatment led to significant improvements in indexes and seizure control in both LKS and ASD populations. In children with LKS and epileptic seizures, the mean ESES index reduction was 49.9 % (±17.7), with 50 % achieving complete seizure control. For children with ASD and epileptic seizures, the mean IED index reduction was 47.2 % (±16.7), with 41 % achieving complete seizure control. Rare side effects were transient and reversible, with no reports of serious adverse events. CONCLUSION: ACTH treatment demonstrates efficacy in reducing ESES and IED indexes and controlling seizures in children with LKS and ASD. These findings underscore the importance of early intervention and careful management of side effects in optimizing outcomes for these patient populations.