Although the effects of dietary glycemic index (GI) on insulin resistance are well documented in adults, the complex interaction among glucose intolerance, inflammatory markers, and adipokine concentration has not been well studied, especially among adolescents. We investigated the effect of a low glycemic index (LGI) diet on insulin concentration, fasting blood sugar (FBS), inflammatory markers, and serum adiponectin concentration among healthy obese/overweight adolescent females. In this parallel randomized clinical trial, 2 different diets, an LGI diet and a healthy nutritional recommendation diet (HNRD) with similar macronutrient composition were prescribed to 50 obese and overweight adolescent girls with the same pubertal status. Biochemical markers FBS, serum insulin concentration, high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and adiponectin were measured before and after a 10 week intervention. Using an intention-to-treat analysis, data from 50 subjects were analyzed. According to a dietary assessment, GI in the LGI group was 43.22±0.54. While the mean for FBS, serum insulin concentration, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and adiponectin concentration did not differ significantly within each group, the average hs-CRP and IL-6 decreased significantly in the LGI diet group after the 10 week intervention (p=0.009 and p=0.001; respectively). Comparing percent changes, we found a marginally significant decrease in hs-CRP in the LGI group compared with the HNRD group after adjusting for confounders. Compliance with an LGI diet may have favorable effect on inflammation among overweight and obese adolescent girls.