Background: Considering the increasing trend of obesity, especially in developing countries such as Iran, and the role of inflammatory factors and insulin resistance (IR) in the occurrence of obesity-related complications as well as the safety of some agents such as folic acid and metformin, this clinical trial was designed to investigate the effect of metformin and folic acid on inflammatory factors and IR among obese children. Materials and Methods: In this randomized, double-blind, controlled clinical trial study, sixty obese children aged 6-12 years were enrolled. Selected obese children were randomly allocated in two interventional (1 mg/daily folic acid or 1000 mg metformin for 8 weeks) groups. Biochemical measurements including homeostasis model assessment of IR (HOMA-IR), homocysteine (Hcy), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured between and within the groups before and after trial. Results: In each group, thirty obese children were studied. The groups were age- and sex-matched. After folic acid and metformin administration, mean of Hcy, HOMA-IR, TNF-α, and IL-8 decreased significantly (P < 0.05). IL-6 decreased significantly after folic acid use (P < 0.05).   Conclusion: The findings of this trial indicated that both metformin and folic acid could decrease IR and level of Hcy in obese children and adolescents. The effectiveness of metformin on IR was more significant than folic acid. Regarding the effectiveness of the two studied agents on inflammatory factors, it is suggested that the role of folic acid was superior to metformin. It is suggested that metformin is a proper agent for obese children with IR and folic acid is an appropriate supplement for obese children with increased inflammatory factors.