The ethanolic extract of Plumbago indica roots (EEPIR) is used anecdotally in Thai traditional medicine for various purposes especially in antibacterial and antitumor treatments. However, its mechanism of action is still unclear. Our previous study indicated that EEPIR was genotoxic at concentrations of 25 – 100 µg/ml and also induced cell cycle delay [1]. We hypothesized that the genotoxicity of EEPIR might potentially support doxorubicin (DXR), a genotoxic chemotherapeutic agent. The chromosomal study was conducted in vitro to investigate the induction of sister chromatid exchange (SCE) level by EEPIR pretreatments at various concentrations, followed by 0.1 µg/ml DXR in human lymphocytes. Results demonstrated that EEPIR pretreatments, in adjunct to DXR, were able to significantly enhance DXR-induced genotoxicity and also delayed the cell cycle. This outcome suggested that EEPIR might be useful for more effective chemotherapy. In addition, the data revealed that the intake of EEPIR should be limited in order to prevent induction of genetic damage from chemical interactions afterwards.