Recently, nanoparticles are emerging as a potential alternative to synthetic pesticides for protection against stored-product insect pests, such as the rice weevil Sitophilus oryzae; however, the toxic effects of nanoparticles on nontarget organisms are not yet understood. Therefore, we investigated the insecticidal effects of synthesized aluminum oxide nanoparticles (Al2O3-NPs) on S. oryzae, as well as their potential toxicity in albino rats. S. oryzae mortality increased as the period of Al2O3-NP exposure increased; 100% mortality was reached at 8000 mg Al2O3-NPs/kg of wheat grain after 7 days of exposure. After 60 days of exposure, all tested Al2O3-NPs concentrations (1000, 2000, 4000, and 8000 mg/kg grain) significantly reduced the number of S. oryzae offspring in a dose-dependent manner. In albino rats, exposure to the LC90 of Al2O3-NPs in a treated diet caused a significant decrease in total body weight and an increase in liver weight in a subacute toxicity test. Moreover, Al2O3-NP treatment elevated the levels of alanine aminotransferase, aspartate aminotransferase, and creatinine in exposed rats relative to control rats, while the uric acid levels of treated rats decreased. Histopathological analysis also revealed various hepatic and renal lesions in treated rats. In summary, although Al2O3-NPs have insecticidal effects, they also have hazardous toxicological effects on rats. Therefore, if Al2O3-NPs are used in the current powder form to protect stored products, they may cause adverse effects to workers and consumers. Further research will be required to develop new nanoformulations with increased safety and potency before these nanoparticles can be used in stored-product pest control.