This work aims to examine the interaction between apo A2 (Apo A-II) –265T > C SNP and dietary total antioxidant capacity (DTAC) on inflammation and oxidative stress in patients with type 2 diabetes mellitus. The present cross-sectional study included 180 patients (35–65 years) with identified Apo A-II genotype. Dietary intakes were assessed by a FFQ. DTAC was computed using the international databases. IL-18 (IL18), high-sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), serum total antioxidant capacity (TAC), superoxide dismutase (SOD) activity and 8-isoprostaneF2α (PGF2α) markers were obtained according to standard protocols. General linear model was used to evaluate the interaction. The interaction of gene and DTAC (PFRAP = 0·039 and PORAC = 0·042) on PGF2α level was significant after adjusting for confounders. A significant interaction was observed on IL18 level (PORAC = 0·018 and PFRAP = 0·048) and SOD (PTEAC = 0·037) in obese patients. Among patients whose DTAC was higher than the median intake, the levels of hs-CRP and PGF2α were significantly higher only in individuals with CC genotype. Serum TAC (PFRAP = 0·030, PORAC = 0·049) and SOD were significantly lower in the CC genotype. There was a favourable relationship between the high-DTAC and SOD (obese: PTEAC = 0·034, non-obese: PFRAP = 0·001, PTRAP < 0·0001, PTEAC = 0·003 and PORAC = 0·001) and PGF2α (non-obese: PORAC = 0·024) in T-allele carriers. The rs5082 SNP interacts with DTAC to influence several cardiometabolic risk factors. Also, we found dietary recommendations for antioxidant-rich foods intake might be useful in the prevention of diabetes complications in the T carrier more effectively than the CC genotype. Future large studies are required to confirm these results.