Introduction of point genetic associations into clinical and laboratory diagnosis will allow the physician to determine the risk of severe diabetes mellitus and its complications with a focus on detection of the genetically determined disorder. The study was aimed to identify the molecular genetic markers of severe diabetic nephropathy in patients with type 1 and 2 diabetes mellitus (DM) based on the GSTP1 (I105V) gene assessment. Genotyping of the GSTP1 gene I105V locus was performed in patients with type 1 and 2 DM. Then we identified the features of oxidative status, free radical oxidation, and renal function in patients with various polymorphic variants of the studied gene. Patients with type 1 DM, who were carriers of the GSTP1 heterozygous polymorphic variant (Ile/Val), showed higher activity of the oxidative stress enzymes (glutathione-S-transferase, catalase) and malondialdehyde compared to homozygous carriers (р < 0.001, р < 0.001, р < 0.05). They also showed a significant increase in the levels of triglycerides (1.6-fold) and the glycated hemoglobin levels (1.1-fold) (p < 0.05). Patients with type 2 DM, who were carriers of the GSTP1 polymorphism homozygous for allele 2 (Val\Val), had a higher level of malondialdehyde (100.5 µmol/L, (р < 0.001)), which was associated with the more severe diabetic nephropathy (average glomerular filtration rate — 48 mL/min/1.73 m2, 24-h urinary albumin excretion — 0.9 g/L; р < 0.01). It has been proposed to assess the GSTP1 (I105V) gene in individuals with type 1 and 2 DM. This polymorphism that is heterozygous in individuals with type 1 DM and homozygous for allele 2 in individuals with type 2 DM is unfavorable in terms of the DM course and complications.