Background/Objectives: The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on plasma concentrations of adiponectin, a fat-derived hormone with anti-atherogenic and anti-inflammatory properties, is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate this association in humans. Methods: RCTs investigating the impact of DPP-4 inhibitors on plasma adiponectin concentrations were identified after searching PubMed-Medline, SCOPUS, and Google Scholar databases (up to February 2015). As quantitative data synthesis methods, the random-effects model and the generic inverse variance method were applied. Standard methods of meta-regression, sensitivity analysis, and publication bias assessments were performed. Results: Eight RCTs with nine treatment-arms were included. Meta-analysis did not suggest a significant pooled effect of DDP-4 inhibitors on adiponectin values (weighed-mean-difference [WMD]: 0.19 μg/mL, 95%CI: -0.50, 0.88). However, a significant elevation of plasma adiponectin concentrations was observed in the subset of trials with vildagliptin (WMD: 0.55 μg/mL, 95%CI: 0.13, 0.98, p=0.010) but not sitagliptin (WMD: -0.06 μg/mL, 95%CI: -1.13, 1.00, p=0.907). There was a significant elevation of plasma adiponectin levels in the subset of trials comparing DPP-4 inhibitors versus placebo or no treatment (WMD: 0.74 μg/mL, 95%CI: 0.36, 1.12, p <0.001) but not in the subset using hypoglycemic drugs as comparators), or using other hypoglycemic drugs (WMD: -0.18 μg/mL, 95%CI: -0.99, 0.62, p=0.654). No significant effect was found for treatment duration, confirmed by meta-regression analyses. Conclusion: DPP-4 inhibitors cause a significant increase in plasma adiponectin concentrations and this effect is greater with vildagliptin than sitagliptin.