Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer agent and immunosuppressant. CLB mutagenicity, teratogenicity, and carcinogenicity are indicated based on their structure and clinical history. This study aims to evaluate the antigenotoxic effect of Cymbopogon citratus essential oil, CC, (75 mg/kg) against CLB (7.5 mg/kg) genotoxicity in rats. GC/MS for essential oil has identified 19 compounds representing approximately 99.7% Geranial was the most abundant (53.5%) followed by Neral (35%) and Myrcene (5.3%).  The lowest was α-Muurolene (0. 1%). The marked damage was observed in total genomic DNA and total protein profile of CLB-intoxicated rat's spleen tissues. Lymphocytes single-strand breaks of treated rats were examined by comet assay after CC had ameliorated these effects in a time-dependent manner (5, 10, and 15 days) for spleen and after 48 hours for lymphocytes. In conclusion, this study suggests that Cymbopogon citrates oil possesses antigenotoxic potential in CLB-intoxicated rats. It can constitute natural, new, and safe co-therapeutics.