We tried to identify the interaction between dietary quality indices and apolipoprotein B Ins/Del and EcoR1 polymorphisms on biochemical and anthropometric factors in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study recruited 700 adults with T2DM in Tehran. The genotypes of Ins/Del and EcoR1 single nucleotide polymorphisms (SNP) were explored via polymerase chain reaction (PCR). Dietary quality index-international (DQI-I), healthy eating index-2015 (HEI-2015) and dietary phytochemical index (DPI) were calculated by semi-quantitative food frequency questionnaire (FFQ). In both crude and adjusted model for confounding factors, we observed significant interactions between DQI-I and Ins/Del SNP on leptin in and 8-iso-prostaglandin F2 α (8-iso-PGF2α), DPI and EcoR1 SNP on total cholesterol (TC) and between Ins/Del SNP and HEI-2015 on interleukin-18 (IL-18). Furthermore, in crude model there were close to meaningful interactions between EcoR1 SNP and DQI-I on total antioxidant capacity (TAC) and between EcoR1 SNP and HEI-2015 on serum leptin and superoxide dismutase (SOD) levels. Our finding indicated that the association between DQI-I, HEI-2015 and DPI with IL-18, TC, leptin and 8-iso-PGF2α in patients with T2DM might be dependent on Ins/Del and EcoR1 variants in ApoB gene.