Cascabela peruviana (L.) Lippold (C. peruviana) has been extensively used for its antifungal and antibacterial properties. However, its role in anti-insect is still under investigation. To investigate the ability of the ethanol extract of C. peruviana against insects, we used the fruit fly (Drosophila melanogaster) as a model to gain more insight into the toxic effects of this extract. We found that the ethanol extract from the stem and leaves of C. peruviana was effective against insects and contained polyphenol and flavonoid compounds. C. peruviana could induce mortality of 2nd-instar larvae and reduce growth and reproduction of fruit flies. Interestingly, the toxicity of C. peruviana extract has been remained to affect the development of the next generation of fruit flies. The locomotor activity and feeding ability of the F1 generation of this insect were significantly reduced by C. peruviana. In addition, flavonoids and polyphenols, as well as saponins and tannins were detected in the ethanol extract of C. peruviana. We assume that the ability of the extract of C. peruviana to control insects may be related to the presence of high levels of these compounds. The findings highlighted that the extract from the leaves of Cascabela peruviana has the potential to be used as an insecticide.