Chromium, selenium, and zinc malnutrition has been implicated in the pathogenesis of diabetic mellitus. This study aims to investigate the effects of novel multiminerals-enriched yeast (MMEY) which are minerals supplementation containing elevated levels of chromium, selenium, and zinc simultaneously in a diabetic animal model. Streptozocin-induced diabetic male Balb/c mice (n = 80) were randomly divided into diabetes control group and three treatment groups. They were administrated oral gavages with low, medium, or high doses of MMEY, respectively. Meanwhile, healthy male Balb/c mice (n = 40) of the same body weight were randomly assigned into normal control group and high dose of MMEY control group. After 8 weeks duration of treatment, the animals were sacrificed by cervical dislocation. Serum glucose concentrations, lipid profiles, oxidative/antioxidant, and immunity status were determined. No significant adverse effects were observed in the high-dose MMEY control group. Treatment of the diabetic mice with medium- or high-dose MMEY significantly decreased serum glucose, triglyceride, total cholesterol, and malondialdehyde and increased high-density lipoprotein cholesterol, glutathione, and the activities of superoxide dismutase and glutathione peroxidase. In addition, MMEY ameliorated the pathological damage of the pancreatic islets, elevated the thymus or spleen coefficient, and increased the expressions of interleukin-2 and -4 in spleen lymphocytes compared with unsupplemented diabetic mice. In conclusion, these results indicate that supplemental MMEY inhibits hyperglycemia, abates oxidative stress, modulates disorders of lipid metabolism, and reduces the impairment of immune function in diabetic mice; especially notable are the protective effects of medium doses of MMEY on the islet cells of diabetic mice.