Background::The hypocaloric diets improve glycemic status in obese individuals, but the response to hypocaloric diets in fat mass and obesity-associated gene ( FTO)-rs9939609 gene variant is unknown. This systematic review and meta-analysis aimed to assess the gene-diet interaction of FTO-rs9939609 gene variant and hypocaloric diets on glycemic control in overweight and obese adults. Methods::Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science, Embase, Scopus, and Google scholar were searched up to December 2018, for relevant clinical trials. Mean changes in fasting blood sugar (FBS), serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were extracted.Results::The pooled analysis of nine studies showed that there was no significant difference between AA/AT and TT genotypes in FBS (weighted mean difference [WMD] = 0.01, 95% confidence interval [CI]: -1.08, 1.10, P = 0.984) and serum insulin (WMD = 0.20, 95% CI: -0.85, 1.26; P = 0.707) after intervention hypocaloric diets. The overweight/obese participants in AA/AT group showed the greatest reduction in HOMA-IR compared with TT genotype following intervention, and this difference was not statistically significant (WMD = -0.38, 95% CI: -0.94, 0.16, P = 0.167). Conclusion::This meta-analysis suggests that there was no significant difference between AA/AT and TT genotypes of FTO-rs9939609 on FBS, serum insulin level, and insulin resistance in response to hypocaloric diets.