This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 40-85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (-1.5 ± 0.7 vs. -0.9 ± 1.2 cm, p = 0.02) and width (-1.4 ± 0.8 vs. -0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (-40.5 ± 71.0 vs. -3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (-8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment-estimated insulin resistance (-3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. -0.002 ± 0.02, p = 0.04) and HbA1c (-0.5 ± 0.8 vs. -0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL-cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. -111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. -35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C-reactive protein (-20.4 ± 24.6 vs. -6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (-0.6 ± 0.9 vs. -0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.