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Background: Numerous genes are involved in immune system modulation, and their polymorphisms may contribute to developing autoimmune disorders. Genetic variation contributes significantly to disease susceptibility to autoimmune thyroid disease (AITD). Objectives: This work aims to investigate the role of single-nucleotide polymorphisms (SNPs) of interferon induced with helicase C domain 1 (IFIH1) rs1990760 and glutamate decarboxylase (GAD) rs769404 in AITD development. Methods: The study had 330 participants, including 153 cases of Hashimoto's thyroiditis (HT), 77 cases of Graves' disease (GD), and 100 healthy controls. All subjects underwent medical history assessment and clinical evaluation. Tests were conducted using real-time PCR, including genotyping of IFIH1 (rs1990760) and GAD (rs769404) via an allele discrimination assay. Results: Most patients with AITD were females. About 18.3% of HT cases and 15.6% of GD cases have a positive family history of thyroid disease. A significant statistical difference was observed between AITD cases and control regarding IFIH1 (rs1990760) and GAD (rs769404) gene polymorphism. Moreover, GD patients, HT patients, and the control group showed increased CT and TT alleles in patients compared to those in controls. Conclusion: IFIH1 and GAD polymorphisms are involved in AITDs (HT and GD) development and are associated with some clinical presentations. HT and GD cases had a positive family history of thyroid disease. There was a significant statistical difference between AITD cases and control regarding IFIH1 (rs1990760) and GAD (rs769404) gene polymorphism. [ABSTRACT FROM AUTHOR]