Metformin (MET) is the first-choice antidiabetic drug for type 2 diabetes mellitus treatment. In this study, the genotoxic potential of MET was evaluated by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) assays in human peripheral lymphocytes as well as comet assay in isolated lymphocytes. Human lymphocytes were treated with different concentrations of MET (12.5, 25, 50, 75, 100, and 125 mu g/mL) for 24 h and 48 h. A negative and a positive control (Mitomycin-C-MMC, 0.20 mu g/mL, for CA, SCE, and MN tests; hydrogen peroxide-H2O2, 100 mu M, for comet assay) were also maintained. MET significantly increased the frequency of CAs at 48 h exposure (except 12.5 mu g/mL) compared to the negative control. MET increased SCEs/cells in both treatment periods (except 12.5 mu g/mL at 24 h). MET only increased the frequency of MN at 125 mu g/mL. While MET significantly increased the comet tail length (CTL) at four concentrations (25, 75, 100, and 125 mu g/mL), it did not affect comet tail intensity (CTI) (except 125 mu g/mL) and comet tail moment (CTM) at all the treatments. All these data showed that MET had a mild genotoxic effect, especially at a long treatment period and higher concentrations in human lymphocytes in vitro. However, further in vitro and especially in vivo studies should be conducted to understand the detailed genotoxic potential of MET.