Herein, nanostructured metal oxides of essential soil nutrient elements (i.e., CuO and CaO) with definite shape and size were simply synthesized, and their pesticidal activities against cotton leafworm (Spodoptera littoralis) were explored for the first time. These metal oxide nanostructures represented novel economic and ecofriendly nanopesticides for sustainable plant protection and might boost the nutrient content of soil. The results showed that CuO nanoparticles (NPs) and CaO NPs exhibited potential entomotoxic effects against S. littoralis. Interestingly, CuO NPs exhibited fast entomotoxic effect with LC50 = 232.75 mg/L after 3 days, while CaO NPs showed a slow entomotoxic effect with LC50 = 129.03 mg/L after 11 days of post-treatments. The difference in the pesticidal activity of the metal oxides is related to their physical characteristics and interfacial surfaces upon insect midgut and cuticle layer of insect body wall. Thus, nanoengineered metal oxides might be utilized to generate an alternative and cost-effective pesticide formulation in the near future.