Abstract Background: The present research aimed to analyze the impacts of magnesium and zinc supplement on the metabolic level in the patients suffering from CHD (coronary heart disease) and T2DM (type 2 diabetes mellitus). Methods: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 55 women suffering from CHD and T2DM. Therefore, the participants have been randomly divided into 2 groups for taking placebo (n = 28) or 250 mg magnesium oxide plus 220 mg zinc sulfate (n =27) or for 12 weeks. Results: Magnesium and zinc considerably declined the levels of fasting plasma glucose (FPG) (β -9.44 mg/dL, 95% CI, -18.30, -0.57; P = 0.03) and levels of insulin (β -1.37 µIU/mL, 95% CI, -2.57, -0.18; P = 0.02). Moreover, levels of HDL-cholesterol have been remarkably enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There have been an association between magnesium and zinc intake and a considerable decrease of C-reactive protein (CRP) (β -0.85 mg/L, 95% CI, -1.26, -0.45; P < 0.001), a considerable enhancement in the total nitrite (β 5.13 µmol/L, 95% CI, 1.85, 8.41; P = 0.003), and total anti-oxidant capacities (TAC) (β 43.44 mmol/L, 95% CI, 3.39, 83.50; P=0.03) in comparison to the placebo. Furthermore, magnesium and zinc remarkably reduced the Beck Depression Inventory index (BDI) (β -1.66; 95% CI, -3.32, -0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (β -1.30; 95% CI, -2.43, -0.16; P=0.02) in comparison to the placebo. Conclusions: In patients with T2DM and CVD the 12-week intake of magnesium and zinc affected FPG, HDL-cholesterol, CRP, insulin, NO, TAC levels, and BDI and BAI score usefully. Trial registration: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered.