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Gene variants of the vitamin D receptor (VDR) have been linked to the alterations of the vitamin D metabolic pathway and thus a candidate risk gene for developing type 2 diabetes mellitus (T2DM). However, the association between VDR gene variants and vitamin D status as well as susceptibility to T2DM in the Ghanaian population have not been explored. This study assessed VDR gene variants, vitamin D status and susceptibility to T2DM. In a 1:1 matched case-control study, 100 clinically diagnosed T2DM patients visiting the Greenshield Hospital at Sefwi Bekwai and 100 apparently healthy non-diabetic controls living in same environs were recruited. Venous blood samples were obtained for biochemical analyses. Lipid profile was estimated spectrophotometrically and serum vitamin D was determined by enzyme linked immunosorbent assay. The variants of the VDR gene were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression models were used to assess the associations between single nucleotide polymorphisms and T2DM. The prevalence of vitamin D deficiency (28.0%) and insufficiency (70.0%) was higher in T2DM than in non-diabetics (5.3% and 44.2%), respectively (p < 0.0001). rs10735810 and rs7975232 was found to increase risk of T2DM under the codominant model (OR = 1.93 (95% CI = 0.69-5.46) and OR = 1.81 (95% CI = 0.51-6.38), respectively), and additive model 1 (OR = 2.02 (95% CI = 0.68-5.98) and OR = 1.29 (95% CI = 0.34-4.84), respectively) whereas rs10735810 and rs7975232 was found to decrease risk of T2DM under the recessive model (OR = 0.96 (95% CI = 0.55-1.67) and OR = 0.58 (95% CI = 0.32-1.02), respectively). Besides, rs7975232 variant was associated with hypertension among individuals with T2DM (p = 0.033). Low vitamin D levels are common in T2DM. There is no association between variants rs10735810 and rs7975232 of VDR gene and T2DM; however, rs7975232 was associated with hypertension and that the 'A' allele of rs7975232 variant seems to be protective against hypertension among T2DM.