Abstract Aim of the study The genotoxic and antigenotoxic potential of the ethanolic extract of Hemidesmus indicus roots were evaluated in cultured human lymphocytes using cisplatin as the positive mutagen. Materials and methods Cytogenetic damage and cytotoxicity were determined in cells exposed to different doses of the extract, ranging from 2 to 32 μg/ml of culture medium, either alone or together with cisplatin. Results There was a significant reduction in cisplatin-induced frequencies of sister chromatid exchanges, chromosome aberrations and micronucleated binucleate cells at the lower concentrations of 4 and 8 μg/ml ( P < 0.05). However, the extract by itself reduced the proliferative rate index, mitotic index and cytokinesis-block proliferative index ( P < 0.05). Further, a significant increase in the percentage of chromosome aberrations was noticed at the higher concentrations. Conclusion Hemidesmus indicus root extract possesses significant genoprotective effect at the lower concentrations although it is cytotoxic and probably genotoxic at higher doses.