The transcription factor 7-like 2 (TCF7L2) gene plays a vital role in glucose and lipid metabolism, with several variants, including rs1790314 and rs12255372, linked to type 2 diabetes mellitus (T2DM). This study aims to evaluate lipid modulation among individuals with T2DM who express the TCF7L2 gene in specific tribes in Nigeria. A descriptive, cross-sectional design was used. Fasting blood samples were collected from 160 T2DM patients attending two tertiary hospitals in the state for routine diabetic check-ups. Standard questionnaires collected data on lifestyle, duration of diabetes, sex, and medication used. Biochemical parameters—fasting blood glucose (FBG), HbA1c, and lipids—were analysed using standard methods. The TCF7L2 variants were genotyped through BigDye Terminator sequencing, with results processed via Bioinformatics Algorithm Trace Edit and aligned with MAFFT. Gene variants and genotype frequencies were estimated by direct gene counting. Biochemical data and TCF7L2 variant results were analysed with GraphPad Prism and Microsoft Excel. The distribution of variants showed a CC genotype for rs1790314 at 32.5%, and a CT/TT mutant at 11.25%. For rs12255372, the GG genotype was observed at 41.25%, with a GT/TT variant at 3.75%. Notably, the use of standard anti-diabetic medications such as biguanides (metformin and Glucophage) and sulfonylureas (Amaryl) was associated with dyslipidemia. Males with T2DM exhibited significant dyslipidemia, characterised by reduced HDL-C and elevated triglycerides (TG), along with increased atherogenic markers like the TC/TG ratio. Additionally, the CT/TT polymorphism of rs1790314 correlated with higher TG, TC/TG ratio, and TC/HDL ratio, as well as decreased HDL-C in T2DM individuals. In summary, subjects expressing TCF7L2 gene variants show associations with dyslipidemia, and T2DM patients with mutant T alleles in both variants had significantly higher levels of HbA1c, lipid parameters, and atherogenic markers among the tribes studied.