The current study investigates the association of the gene expression and Polymorphism of the TCF7L2 gene variations (rs78025551 and rs7903146) with increased incidence of type 2 diabetes mellitus (T2DM) in Iraqi patients. The study included 200 participants; 100 were T2DM patients, and 100 were healthy controls. Sex, age (divided into three groups), BMI, fasting blood glucose (FBG), and HbA1c % were investigated. Results indicated that there were substantial variations between patients and controls (p < 0.01) regarding age, age group, BMI, FBG, and HbA1c %, while no significant differences at the sex level. The first part of the research revealed the determination of TCF7L2 gene expression. The median of gene expression (ΔCt) of the TCF7L2 gene in patients' was (9.36), compared to the control (10.14); statistically, there were no significant differences (p =0.2) between the studied groups.  Moreover, the median of fold change in gene expression (2-ΔΔCt) revealed up-regulation at (1.54). In the second part, two SNPs with polymorphic frequencies (rs78025551, [C/G] and rs7903146 [C/G/T]) were assigned in the DNA sequence of the PCR-amplified region (943 bp). It was found that highly statistically significant differences between T2DM patients in all genotypes and alleles of rs78025551 and rs7903146 in comparison with controls. The data pertaining to rs78025551 revealed notable genotype frequencies; there was a significant difference between genotypes GG in T2DM patients in comparison with control groups (p > 0.049). T2DM patients had a 4% GG genotype and an odd ratio of 8.60 (1.18-62.67). T2DM can manifest when people possess a homozygous mutant GG. The SNP's G allele was found in (24%) of T2DM patients and (17%) of healthy controls with a p-value of 0.01 (OR = 1.35, 95%CI = (0.95- 2.49)) suggesting a potential association with T2DM. This study identified an additional single nucleotide polymorphism (SNP) that exhibited association with T2DM. The study revealed a notable correlation between the rs7903146 single nucleotide polymorphism (SNP) and the occurrence of T2DM disease in individuals possessing heterozygote (CT) genotypes. The rs7903146 genotype frequency in the T2DM and control groups was 60% and 45%, respectively. The genotype of rs7903146, specifically the heterozygous CT genotype, exhibited a significant association with T2DM. The odds ratio (OR) for the CT genotype was 2.63. The SNP's T allele was detected in (48%) of T2DM patients and (32.5%) of healthy controls, with a p-value of 0.006.