BACKGROUND This study evaluated the effects of zinc supplementation on glycemic control, other cardiometabolic and anthropometric parameters, and disease progression in prediabetes. METHODS A randomized double-blind placebo-controlled Phase 2 clinical trial was conducted over a 12-month period in 200 subjects (43% male; mean [± SD] age 51.8 ± 7.3 years), randomly assigned (1:  1) to the treatment or control group. The treatment group received zinc (20 mg daily). Subjects were evaluated at baseline and at 1, 3, 6, and 12 months. The primary outcome was the change in glycemic control from baseline. Multiple regression analyses were performed, with change in outcome variables after intervention from baseline used as continuous dependent variables. RESULTS In both groups, mean serum zinc concentrations prior to the trial were below normal (15.29-21.41 μmol/L). During the 12-month follow-up, a significantly higher percentage of participants developed type 2 diabetes in the control compared with zinc-treated group (25.0% vs 11.0% respectively; P = 0.016). Fasting plasma glucose (FPG), 2-h glucose levels in the oral glucose tolerance test (OGTT), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in the treated group, with significant improvement in β-cell function. In all four regression models, the best predictor of the dependent variables (i.e. change in FPG, 2-h glucose in the OGTT, HOMA-IR, and homeostatic model assessment of β-cell function) was zinc treatment. CONCLUSIONS Zinc supplementation reduced blood glucose and insulin resistance while improving β-cell function. Furthermore, supplementation reduced disease progression to diabetes and had beneficial effects on TC and LDL-C.