Introduction: This study aims to investigate the correlation between interleukin-6 (IL-6) (-174 G>C) and tumor necrosis factor-alpha (TNF-α) (-238 G>A) cytokine gene polymorphisms and diabetic foot infection (DFI). Materials and Methods:This study involved the collection of blood samples from a total of 207 participants who were grouped as follows: a control group of 60 healthy individuals, a group of 60 patients with type 2 diabetes mellitus (T2DM) but without diabetic foot ulcer (DFU), and a group of 87 patients with DFI.The genotypes of IL-6 (-174 G>C) and TNF-α (-238 G>A) polymorphisms were determined using real-time PCR and the TaqMan method. Results:The findings indicate that there were no statistically significant variations in the distribution of IL-6 (-174 G>C) and TNF-α (-238 G>A) polymorphisms genotypes among individuals with T2DM who had DFI, individuals with T2DM without DFU, and the control group (p> 0.05).A higher prevalence of osteomyelitis was detected in patients with DFI possessing the GG genotype (53.1%) of the IL-6 (-174 G>C) polymorphism, compared to those with the mutant genotypes (GC + CC) (28.9%) (p= 0.024).The study revealed a higher prevalence of venous insufficiency (VI) in individuals with DFI possessing TNF-α (-238 G>A) GA genotype compared to those with the GG genotype (80.0%, 24.4%, respectively) (p= 0.007).The study indicated that patients with DFI possessing the TNF-α (-238 G>A) GA genotype had a higher mean body mass index (BMI) compared to those with the GG genotype (p= 0.012). Conclusion:The study has demonstrated that the IL-6 (-174 G>C) and TNF-α (-238 G>A) polymorphisms cannot serve as reliable indicators for determining an individual's vulnerability to DFI and T2DM.The IL-6 (-174 G>C) polymorphism's GG genotype exhibited a significant association with osteomyelitis in patients with DFI.Findings suggest that individuals with the TNF-α (-238 G>A) GA genotype in DFI patients may experience VI and higher average BMI than patients with the GG genotype.