In type 2 diabetes mellitus (T2DM), hyperglycemia leads to oxidative insult. Vitamins A and E have antioxidant potentials and may help in managing diabetes. The combined effect of high-dose vitamin A plus E supplementation with and without zinc on T2DM, has never been examined. Thus, this study aimed to evaluate and compare the effect of high-dose vitamin A plus E supplementation (AE) versus high-dose vitamin A plus E with zinc (AEZ), on different diabetic parameters. Ninety-eight patients with T2DM were randomized to receive either: 50,000 IU vitamin A and 100 mg vitamin E (AE group, N = 36), an equivalent dose of vitamin A and E combined with 25 mg zinc (AEZ group, N = 35), or no supplements (control group, N = 27) for three months. Compared to control, AEZ group showed significant reductions in fasting blood glucose, 2 h postprandial blood glucose, and glycated hemoglobin (HbA1c) with significant increases in homeostasis model assessment of beta-cell function and difference value of fasting insulin. Two hair loss cases were recorded in both treated groups. Although vitamin A needs dose moderation, these results suggest that, high-dose vitamin A plus E supplementation combined with zinc may improve glycemic control, β-cell function, and insulin secretion in adults with T2DM.