Montelukast sodium (MS) is a leukotriene receptor antagonist and used clinically as an antiasthma agent. MS has been hypothesized to have adverse effects in insects. To test this hypothesis, MS was added to the artificial diet of the fruit fly Drosophila melanogasterMeigen (Diptera: Drosophilidae) at different concentrations (1200, 1600, 2000, and 2400 mg/L) under laboratory conditions. The effects of MS on the survival rate and development time of D. melanogaster, as well as its effects on malondialdehyde (MDA) levels and cytochrome P450 monooxygenase (CYP450) enzyme activity in adults were investigated. The genotoxic effect of MS in whole adults was examined using a single-cell gel comet assay. Compared with the control, dietary MS concentrations led to decreased survivorship in each developmental stage of the insects. MDA content was significantly higher in adults reared on MS diets at 2400 mg/L. In addition, low MS concentrations significantly decreased CYP450 enzyme activity in the adults. MS resulted in significantly more DNA damage. This study confirms that oxidative stress and DNA damage are induced by dietary exposure to MS in D. melanogaster adults, adversely affecting survivorship. These findings have important implications in the control of agricultural pest insects.