To determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6, and IL-10 in subjects with prediabetes, inflammation, and hypomagnesemia, a total of 26 subjects men and non-pregnant women were included and randomly allocated to receive 30 ml of MgCl(2) 5% solution (equivalent to 382 mg of magnesium) or placebo, daily during three months. At baseline conditions, there were not significant statistical differences between the groups. At end of the study, hsCRP levels were significantly lower in the intervention group (3.3 ± 2.5 vs 8.0 ± 5.9 mg/L, p = 0.03), as compared with the control group. However, the intra-group analysis of the individuals who received magnesium, did not shows significant statistical differences between baseline and final conditions (4.1 ± 3.0 and 3.3 ± 2.5, p = 0.45). In addition, TNF-alpha (1.2 ± 0.3 vs 1.1 ± 0.3 pg/mL, p = 0.69), IL-6 (0.3 ± 0.3 vs 5.0 ± 7.7 pg/mL, p = 0.08), and IL-10 (1.8 ± 0.4 vs 1.8 ± 0.5 pg/mL, p = 0.89) serum levels were not significantly different between the groups. Our results do not show a beneficial effect of oral magnesium supplementation on hsCRP, IL-6, TNF-alpha, and IL-10 levels in prediabetic subjects with hypomagnesemia and inflammation. Further studies with large sample sizes and longer time of follow-up are necessaries to verify the results of our pilot study.