Solanum mammosum (L.) is known as a poisonous plant and has been extensively used for anti-cancer, antifungal, antibacterial properties. However, the effectiveness of Solanum mammosum against insects has not been fully reported yet. To assess the ability of Solanum mammosum fruit extract against insects, we used fruit fly (Drosophila melanogaster) as a model. In this study, our results showed that phytochemicals and many secondary metabolites were present in Solanum mammosum fruit extracts such as alkaloids, saponins, tannins, terpenoids, coumarins, cardiac glycosides, steroids-triterpenoids, flavonoids, and phenolic compounds. The total polyphenol and flavonoid content were also determined to be 275±1.89 mg GAE/g extract and 676±5.14 mg QE/g extract, respectively. Besides, Solanum mammosum fruit extract caused lethal to 2nd instar, reduced a pupae formation rate of Drosophila larvae. Interestingly, Solanum mammosum extract is more effective in the suppression of pupae eclosion than Ascend as a commercial pesticide. These phenomena might be associated with reduced accumulation of energy, including carbohydrates, lipids, and protein. In addition, the activities of esterases and phosphatases were inhibited in Drosophila by the intake of Solanum mammosum. The study concluded that Solanum mammosum has great potential as an insecticidal agent.