OBJECTIVE Previous studies suggested that dyslipidemia was potentially associated with anti-diabetic medications of sulfonylureas (SUs). The results were, however, inconsistent. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effects of SUs on the level of lipids in patients with type 2 diabetes mellitus (T2DM). METHODS We searched PubMed, EMBASE, and CENTRAL databases for RCTs that addressed the effects of second- and/or third-generation SUs used in T2DM patients on lipids profiles with study duration of at least 12 weeks. Two reviewers independently screened literature, collected data, and assessed methodological quality of included studies. The meta-analysis was performed by using the RevMan5.1 software. RESULTS A total of 59 RCTs were included, of which 52 were included for final meta-analysis. The results suggested that SUs statistically increased the levels of FFA (SMD = 0.24, 95%CI 0.06 to 0.42) and TG (MD = 0.06, 95%CI 0.02 to 0.10), but decreased HDL-C (MD = -0.07, 95%CI -0.11 to -0.04) and LDL-C (MD = -0.11, 95%CI -0.17 to -0.04); but the SUs had no effect on TC (MD = 0.01, 95%CI -0.05 to 0.08), ApoA1 (MD = 0.01, 95%CI -0.03 to 0.04), and Apo B (MD = -0.01, 95%CI -0.05 to 0.03). When compared to metformin, SUs could increase TC and LDL-C; compared to glinides, SUs increased TC and lowered HDL-C; compared to thiazolidinediones, SUs reduced TC, LDL-C, HDL-C, and increase TG. CONCLUSIONS SUs have a small effect on lipids, although they may statistically increase the level of FFA and TG, and decrease LDL-C and HDL-C.