Chlorantraniliprole and indoxacarb insecticides exhibit good efficiency for control lepidopteran pests. The current study is a comprehensive analysis of the effect of lethal and sublethal concentrations of these insecticides on Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae) by using the leaf dipping technique. The LC50 values ranged from 0.06 to 1.07 mg/L, and 0.005 to 0.81 mg/L for chlorantraniliprole and indoxacarb, respectively. Our results showed that the treatment of the 2nd instar larvae with LC50 concentrations of these insecticides significantly increased the length of larval and pupal duration as well as pupal weight in most cases. While, no significant differences have been found in the percentage of hatchability except for LC50 equivalent of indoxacarb. Female behavior regarding calling activity decreased by 50–60% following exposure to the LC50 concentration of both insecticides. Gas chromatography analysis results showed that both insecticides lowered pheromone titer except at chlorantraniliprole LC50 equivalent for (Z,E)-9,12-tetradecadien-l-ol acetate, and indoxacarb LC10 equivalent for (Z)-9-tetradecenyl acetate. Additionally, the activity of mixed-function oxidases and glutathione S-transferase were elevated relative to control. The carboxylesterase activity significantly increased when assayed with both chlorant-raniliprole concentrations and indoxacarb LC10 equivalent. These results indicate that chlorantraniliprole and indoxacarb could be effective for S. littoralis control