Diabetic foot ulcer (DFU) or Lower limb ulcers are one of the major complications caused by diabetes mellitus especially when patients fail to maintain tight glycemic control. DFU is linked to multiple risk factors along with the genetic factors and ethnicity which play a significant role in the development of DFUs through their effects on multiple aspects of the pathophysiological process. This narrative review aimed to summarize all the previous studies within the last ten years associating gene polymorphism and DFU. Polymorphism associated with vascular endothelial growth factor (rs699947), the G894T polymorphism of the endothelial nitric oxide synthase gene, interleukin-6–174 G>C gene polymorphism, heat shock protein 70 gene polymorphism, the apolipoprotein E gene polymorphism, Sirtuin 1 (sirt1) polymorphisms (rs12778366 and rs3758391), hypoxia-inducible factor -1 alpha exon 12 mutation, toll-like receptor gene (thr399ile polymorphism), the effect of both monocyte chemoattractant protein-1 (MCP-1) –2518A/G and the vascular endothelial growth factor (VEGF) –634g/c polymorphisms were summarized in this review. The results of all these studies indicating that screening for Polymorphisms might be helpful for early screening and prevention of DFU through their regulatory function on the transcription activity of the genes. Additional studies should be conducted in larger and different populations and ethnic regions to confirm the results of all previous studies mentioned in this review.