Background and Objectives: Peroral supplementation with trivalent-chromium (Cr) or magnesium (Mg) has been shown to improve insulin resistance (IR). The objective of this study was to determine whether combined peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone. Methods and Study Design: Subjects (n=120, age range 45-59 years old) and diagnosed with IR were randomly divided into four groups and monitored for a period of 3 months: group 1 (the placebo control group), group 2 (160 μg/d Cr), group 3 (200 mg/d Mg), and group 4 (160 μg/d Cr plus 200 mg/d Mg). Fasting blood glucose (FBG), fasting insulin (FIns), erythrocyte Cr and Mg content, and glucose-transporter-4 (GLUT4) and glycogen-synthase-kinase-3β (GSK3β) mRNA levels in activated T-lymphocytes were measured, and insulin resistant index (IRI) was calculat- ed. Results: Significant decreases between the baseline and study conclusion values of FBG (0.37 mmol/L, p<0.01), FIns (2.91 μIU/mL, p<0.01) and IRI (0.60, p<0.01) were observed in group 4, but not groups 1-3. Simi- larly, compared with baseline, significant changes in GLUT4 (2.9-fold increase, p<0.05) and GSK3β (2.2-fold de- crease, p<0.05) mRNA levels in activated T-lymphocyte were observed at the study’s conclusion in group 4, but not in groups 1-3. Conclusions: Our results indicate that combining peroral supplementation with Cr and Mg im- proves IR more effectively than Cr or Mg alone, and this may be attributable to increased induction and repres- sion, respectively, of GLUT4 and GSK3β expression.