Background: Epilepsy is a common serious neurological disorder. Medical histories and electroencephalogram (EEG) are not always sufficient for epilepsy diagnosis; therefore, exploring novel methods for the accurate diagnosis of epilepsy is of great importance. Recent studies indicate that Matrix metalloproteinases (MMPs) especially MMP-2 is sensitive to seizures thus; MMP-2 may be a potential biomarker for epilepsy diagnosis. Subject and method: Thirty four epileptic patients older than 2 years subjected to: Detailed medical history, general and neurological examination, routine laboratory studies, EEG , Brain magnetic resonance imaging (MRI), and serum MMP-2 level measurement . Thirty four age and sex matched healthy controls were selected and their serum MMP-2 were obtained. Results: serum MMP-2 levels were statistically significantly low in patient with idiopathic epilepsy compared to control group .Levels were less in patient with focal epilepsy than those with generalized epilepsy.Serum MMP-2 was lower in drug resistant epileptic patients and highest in newly diagnosed patients with negative correlation observed between duration of epilepsy and MMP-2 levels. Sensitivity of MMP-2 as biomarker was 85.29% with 97.06 % specificity. Conclusion: MMP-2 levels decreased in patients with epilepsy especially those with focal seizures. This tool may be a helpful diagnostic biomarker for epilepsy with a good sensitivity and specificity.