Different parts of the plant Coleus forskohlii (Willd.) Briq. (Lamiaceae) were used in traditional medicine. Its roots and leaves are the only known natural source of the labdane diterpene forskolin which has multiple biological activities. The present study was aimed to evaluate the in vivo ability of forskolin to protect DNA against ethyl methanesulphonate (EMS)-induced DNA damage in somatic cells of third instar larvae of Drosophila melanogaster using comet assay. A statistically significant increase in the DNA damage was observed only in the larvae treated with the 1 mM EMS in comparison to the negative control group. Forskolin in different concentrations (0.5, 1, and 2 mg/mL of standard food) showed significant DNA protective activity in presence of EMS as DNA damaging agent. The greatest ability to protect the DNA against EMS was observed following co-treatment with the lowest concentration of forskolin plus EMS with a percentage reduction of 94.2. These findings suggest that the forskolin could be used in preventive therapy against diseases associated with DNA damage.