BACKGROUND: Gastroesophageal reflux disease (GERD) is a common chronic condition characterized by abnormal reflux and regurgitation of stomach contents into the esophagus. Its prevalence is increasing worldwide and poses a high economic burden. AIM: To explore the potential correlation between galectin-1, galectin-3, galectin-8, galectin-9, and GERD, highlighting their potential role as biomarkers in disease diagnosis, and pathogenesis. MATERIALS AND METHODS: A prospective cross-sectional study was conducted on 40 patients with GERD disease and 40 healthy control subjects from January 2023-May 2024 at Al-Kindy Teaching Hospital-Gastroenterology Unit. Venous blood was collected from patients and controls. Serums of both groups were quantified for galectin-1, galectin-3, galectin-8, and galectin-9 using a human ELISA kit. RESULTS: Galectin-1 showed no statistically significant difference in the median levels between patients with GERD and controls (p = 0.567). A significant difference was found in the median levels of galectin-3, with higher levels in patients with GERD compared to controls (p = 0.0037). The most significant was galectin-3, AUC = 0.684 (95% CI: 0.570-0.784), p = 0.003, had a significant moderate discriminatory ability in differentiating between patients with GERD and healthy controls with cutoff value <
13.682, sensitivity = 74.4%, specificity = 55%, and accuracy = 61.7%. CONCLUSIONS: This study suggests that serum galectin-3 is the best potential noninvasive diagnostic biomarker for the prediction and identification of GERD.