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Background: Several neuropeptides have concerned with epilepsy pathogenesis; ghrelin showed an anticonvulsant effect. There is a potential relation between its level and antiepileptic drug (AEDs) response. Objective: To evaluate ghrelin effect in adult epileptic patients and in response to AEDs. Materials and methods: This case control study included 40 adult epileptic patients and 40 healthy controls. Participants were subjected to history taking of seizure semiology, full general and neurological examination, electroencephalography, and cranial imaging. Fasting serum acylated ghrelin (AG), unacylated ghrelin (UAG), and urine AG levels were estimated to all participants by enzyme-linked immunosorbent assay (ELIZA). Results: Serum AG, UAG, and urine AG levels were statistically higher in epileptic patients than controls (p = 0.005, 0.003, and 0.018 respectively). A significant higher level of serum AG was found among generalized epileptic patients (p = 0.038). There was higher statistically significant levels of all measured parameters among poly therapy patients (p = 0.003, 0.013, and 0.001 respectively). Also, a higher statistical significant level of serum AG and UAG in AEDs-responsive patients was found (p < 0.001). Our results demonstrated significant positive correlation between all measured parameters (serum AG, UAG, and urine AG) and epilepsy duration (p = 0.001, 0.002, and 0.009 respectively). High serum AG and UAG levels were independently associated with longer epilepsy duration (p = 0.00 and 0.008) and better response to AEDs (p < 0.001). Conclusion: These results indicated that serum AG and UAG levels were significantly high in epileptic patients especially with prolonged epilepsy duration and good AEDs response. Trial registration: ClinicalTrials.gov NCT03926273 (22-04-2019) "retrospectively registered." [ABSTRACT FROM AUTHOR]