This study was designed to evaluate the effect of the sub sterilizing dose of gamma radiation (70Gy) and LC₅₀ of three benzothiophene derivatives on the lipid peroxidation content as an oxidative stress biomarker and on the antioxidants response (glutathione –S-Transferase (GST) activity and glutathione reduced level (GSH) in 4^th instar larvae of F₁ and normal Spodoptera littoralis larvae. The results revealed that both gamma radiation and the three benzothiophene derivatives induced a significant decline in the GST and GSH which was remarkable in F₁ larvae resulted from irradiated male parent pupae with 70Gy and feed on treated leaves with the first derivative. In contrast, the MDA exhibited a significant elevation which also was pronounced in F₁ larvae resulted from irradiated male parent pupae with 70Gy and feed on treated leaves with the first derivative. Consequently, it could be concluded that the three derivatives and their combination with gamma radiation disturbed the physiological balance Spodoptera littoralis which lead to larval mortality and can use them as an integrated control program for S. littoralis.