Etoposide (ETZ) is a standard drug used in treatment of several malignancies. However, it is associated with increased risk of spleen damage and secondary acute myeloid leukaemia. Ginger (Zingiber officinale) is an ancient safe remedy used in management of minor health issues due to being rich in active constituents. Therefore, we hypothesize that ginger oil can ameliorate ETZ-induced oxidative stress and DNA damage in spleen tissues and leukocytes. To achieve our aim, ginger oil (75&150 mg/kg b.w.) was administered three times to male albino rats an hour prior to ETZ oral administration (1mg/kg b.w.) for 3 weeks. Results showed that ETZ induced marked biochemical alterations in the oxidative status of spleen tissues. The elevated lipid peroxidation and nitric oxide levels were statistically countered. However, the glutathione, superoxide dismutase and catalase enzymes were reduced. Moreover, the DNA single strand breaks as evaluated by comet assay in blood leucocytes also showed significant changes. The administration of ginger oil caused significant improvement of oxidative stress status and DNA damage. In conclusion, our results suggest that ginger oil could be used as a herbal remedy for reducing ETZ-induced adverse effects in male albino rats.