Purpose: To assess whether serum calponin-3 could serve as a biomarker for epilepsy. Method: We collected serum samples from 242 subjects, including 157 patients with epilepsy and 85 healthy control subjects. The levels of serum calponin-3 were determined using enzyme-linked immunosorbent assay kits (ELISA), and their correlation with epilepsy clinical characteristics was analysed statistically. We used the upper limit of the 95% confidence interval (CI) when dividing epilepsy patients into normal and elevated groups based on serum calponin 3 levels in controls. The receiver operating characteristic (ROC) curve was used to determine the diagnostic efficiency.