The aim of the present meta-analysis was to investigate the long-term effects of glycemic index-related diets in the management of obesity with a special emphasis on the potential benefits of low glycemic index/load (GI/GL) in the prevention of obesity-associated risks.Electronic searches for randomized controlled trials (RCTs) comparing low glycemic index/load versus high glycemic index/load diets were performed in MEDLINE, EMBASE and the Cochrane Library. Outcome of interest markers included anthropometric data as well as biomarkers of CVD and glycemic control. Study specific weighted mean differences were pooled using a random effect model. 14 studies were included in the primary meta-analysis. Weighted mean differences in change of C-reactive protein [WMD: -0.43 mg/dl, (95% CI -0.78 to -0.09), p = 0.01], and fasting insulin [WMD: -5.16 pmol/L, (95% CI -8.45 to -1.88), p = 0.002] were significantly more pronounced in benefit of low GI/GL diets. However decrease in fat free mass [WMD: -1.04 kg (95% CI -1.73 to -0.35), p = 0.003] was significantly more pronounced following low GI/GL diets as well. No significant changes were observed for blood lipids, anthropometric measures, HbA1c and fasting glucose. Sensitivity analysis was performed for RCTs excluding subjects with type 2 diabetes. Decreases in C-reactive protein and fasting insulin remained statistically significant in the low GI/GL subgroups.The present systematic review provides evidence for beneficial effects of long-term interventions administering a low glycemic index/load diet with respect to fasting insulin and pro-inflammatory markers such as C-reactive protein which might prove to be helpful in the primary prevention of obesity-associated diseases.