Mutations that occur through DNA strand breaks are the prerequisites for the development of tumors, which ultimately leads to various genetic disorders including cancer. A number of naturally occurring compounds including certain dietary constituents play an important role in causation and prevention of a number of genetic diseases. Diallyl sulfide (DAS), a volatile organosulfur compound present in garlic has been shown to possess various pharmacological effects including cancer preventive properties. Now we are reporting the antimutagenic properties of DAS on 7,12- dimethylbenz[a]anthracene (DMBA), a carcinogenic polycyclic aromatic hydrocarbon, induced DNA strand breaks in mouse skin, using an alkaline unwinding assay. DAS (2.5–10 mg/kg body-weight) was applied topically, prior and post to DMBA (5 mg/kg body-weight) at the sampling time of 24, 48, 72 and 96 h. DAS application resulted in a significant (p < 0.001) protection in DMBA-induced DNA strand breaks. The pre-treatment of DAS (10 mg/kg body-weight) showed 68.35% protection and post-treatment showed 59.49% protection, at an intermittent period of 48 h, against DMBA-induced DNA strand breakage. These findings suggest that DAS can effectively check the mutations induced by environmental toxicants.