Background Glucagon like peptide-1 receptor (GLP-1R) agonist usage has previously been linked to an elevated incidence of thyroid cell adenomas and carcinomas in animals. Aim The goal of this study was to determine if there was an association between GLP-1R gene polymorphism and expression with the risk of papillary thyroid carcinoma (PTC) and its clinical characteristics among the Egyptian population. Material and methods A total of eighty PTC patients and eighty healthy controls were included in the study. Real-time polymerase chain reaction (real-time PCR) and immunohistochemistry were used to determine GLP-1R expression in tumor tissue. The polymorphisms rs1042044 and rs6923761 in the GLP-1R gene were determined using PCR -restriction fragment length polymorphism (PCR-RFLP). Results PTC patients exhibited considerably greater frequencies of rs1042044 AA genotypes and A allele than controls (OR (95% CI) = 4.5 (1.75–11.8), P < 0.001; OR (95% CI) = 2.032 (1.301–3.17), P < 0.001 respectively). GLP-1R mRNA and protein expressions were higher in tumor samples than normal thyroid tissues among PTC patients. In addition, high GLP-1R expressions were more common in rs1042044 AA genotype carriers than CC carriers (P < 0.001). GLP-1R mRNA expression showed 95 % sensitivity and 97% specificity for PTC diagnosis. Moreover, GLP-1R expression was closely associated with LN metastasis, tumor size, tumor stage, and multifocality in PTC patients. Conclusion This research provides new evidence linking the GLP-1R genetic polymorphism and tissue expression to PTC risk and invasiveness among the Egyptian population.