Aims: This study aimed to provide evidence on the levels of circulating irisin in patients with type 2 diabetes mellitus (T2DM). Methods: A meta-analysis was conducted to compare the irisin levels in patients with T2DM with the levels in control patients. PubMed, Embase, CENTRAL databases, and other sources were searched from inception through September 2020. Review manager software version 5.4 was used to calculate the pooled outcomes. Heterogeneity was measured using I-2 statistics. Results: Twenty-six studies involving 3667 participants met the inclusion criteria and were analyzed in this study. We found that irisin levels were significantly lower in patients with T2DM [Standard (Std.) Mean Difference, -1.02; 95% confidence interval (95% CI), -1.37 to -0.67; p < 0.00001]. Sensitivity analysis confirmed the robustness of this result (Std. Mean Difference, -0.56; 95% CI, -0.73 to -0.39; p < 0.00001). Conclusions: As compared to the control group and irrespective of differences in ethnicities, age groups, study designs, blood samples, sample sizes, language used for the study, or ELISA kits, lower levels of irisin were observed in patients with T2DM. (C) 2021 Elsevier B.V. All rights reserved.