In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have healthbenefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms ofits action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated thegenotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assayin human lymphocytes. Results have shown that all treatments with EEPIR (12.5-100 μg/ml) could induce cellcycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither inthe second nor the third cell cycle. Only at concentrations of 25, 50, and 100 μg/ml were SCE levels significantlyincreased above that of the control (p<0.05) . EEPIR at a concentration of 500 μg/ml induced cell death as fewmitotic cells were shown. Accordingly, EEPIR (25-100 μg/ml) is genotoxic in human lymphocytes and cytotoxic atconcentrations of ≥500 μg/ml in vitro. Therefore, these activities of the EEPIR could serve its potential therapeuticeffects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitroevidence.