Commiphora gileadensis (Arabian balsam) is a wild medicinal plant naturally distributed in Saudi Arabia. To study the effect of habitat variation on the plant chemical compositions, chromatography/mass spectrometry (GC–MS) was applied on the C. gileadensis gathered from two regions (Khulais and Breiman). In addition, the antigenotoxic activity of C. gileadensis were examined by evaluating chromosomal aberrations observed in bone marrow cells, DNA fragmentation in hepatocytes and sperm abnormalities assays in mice. Animal were treated as follow: groups treated with: CCL4 (1.2 mL/kg), high dose of C. gileadensis (400 mg /kg b.w.), low dose of C. gileadensis (200 mg /kg b.w.), CCL4 plus high dose of C. gileadensis, CCL4 plus low dose of C. gileadensis. The results monitored a significant difference between the chemical constitutive of C. gileadensis extracts in the studied regions. In vivo experimentations showed that pretreatment with the tested doses of C. gileadensis succeeded to reduced CCL4 induced injuries. A more efficient protective activity was obtained with implementation of the plant extract at high dose. Thus, the results reflect that the variation in geographical location affect on the chemical compositions of the plant and that C. gileadensis is a promise candidate which could protect against CCL4 induced genotoxicity.