Aim to improve the effectiveness of early diagnosis, prediction and therapy of distal neuropathy (DN) and diabetic foot syndrome (DFS) in patients with type 1 and type 2 diabetes by identifying the features of gene polymorphism of xenobiotic biotransformation systems and antioxidant protection, pro- and anti-inflammatory cytokines. Material and methods. The study group included 150 patients aged from18 to 70 years, men and women with type 1 and type 2 diabetes, having DN and DFS, and 20 healthy people. Research methods used in the study: 1) clinical objective research; 2) molecular genetic methods; 3) population-statistics methods. Results. In patients with type 1 and type 2 diabetes with DN and DFS, the significant differences were found between the frequency of occurrence of polymorphism variants: G681A(*2) the CYP2C19 gene (2 = 9.642, p = 0.008), (OR = 0.334, (95% CI 0.145-0.768)); A8202G of the MMP9 gene (2 = 7.589, p = 0.022), (OR =0.476, (95% CI 0.226-1.005)); IIe105Val of the GSTP gene (2 = 19.521, p = 0.000), (OR = 0.174, (95% CI 0.070-0.435)); G-1293C(c1/c2) of the CYP2E gene (2 = 15.996, p = 0.000), (OR = 0.163, (95% CI 0.034-0.772)). Conclusion. Among patients suffering from type 1 and type 2 diabetes with the genotype A/A polymorphism G681A(*2) of the CYP2C19 gene, the DN and SDS are 4 times more likely to develop. The G/G polymorphism genotype A8202G of the MMP9 gene increases the risk of developing DN and DFS by almost 2 times. The genotype G/G polymorphism IIe105Val of the GSTP gene in patients increases the risk of developing DN and DFS by 4 times. The variant of the genotype C/C polymorphism G-1293C(c1/c2) of the CYP2E gene increases the risk of DN and DFS by 5 times.