In individuals with type 2 diabetes mellitus (T2DM), the cannabinoid receptor 1 (CNR1) gene polymorphism has been linked to diabetic nephropathy (DN). Different renal disorders, including DN, have been found to alter cannabinoid (CB) receptor expression and activation. This cross-sectional study aimed to investigate the relationship between CNR1 rs1776966256 and rs1243008337 genetic variants and the risk of developing DN in Iraqi patients with T2DM. The study included 100 patients with T2DM, divided into two groups: 50 with DN and 50 without DN. Genotyping of CNR1 rs1776966256 and rs1243008337 polymorphisms was conducted using PCR in DN patients and control samples. The distribution of rs1776966256 and rs1243008337 genotypes and alleles between the two groups revealed statistically significant differences. The frequencies of the GG and AG genotypes of CNR1 rs1776966256 were significantly different between DN patients and the control group. Additionally, compared to the A allele, the G allele of this polymorphism was linked to a higher incidence of DN (p=0.0001). Patients with the genetic polymorphism rs1243008337 had higher genotypes of CC and AC and were more likely to develop DN in the polymorphism genotype than the wild genotype. Additionally, compared to the A allele, the C allele was linked to a higher chance of developing DN (p=0.0001). Both rs1776966256 and rs1243008337 polymorphisms were correlated with the development of diabetic nephropathy.