Resistance ratio (RR) and biochemical alterations for seven bioinsecticides against Spodoptera littoralisin two Egyptian governorates were assayed. The values of LC₅₀ have fluctuated from 42.9 to 0.01 ppm for the strain of Menofia governorate, but in Gharbia governorate the values have fluctuated from 0.004 to 0.1 ppm. On the other hand, RR for the examined insecticides: Radeiant^®, Agrine^®, DipelDF^®, Dipel 2X^®, Brotecto^®, Radecal^® and Biotect^® during 2019 cotton season. Resistance ratio (RR) for seven insect growth regulators (IGR's) Demelen^®, Tobron^®, Demeron^®, Kabres^®, Kalegron^® and Match^® against S. littoralis were also assayed. LC₅₀ values in Menofia governorate have fluctuated from 0.014 to 2.9 ppm, and RR values were very low. Finally these compounds still effective against S. littoralis during 2019 season. Alterations were induced in enzymes: acetylcholinesterase (AChE), glutathione-S- transferase (GST), acid and alkaline phosphatase as well as total protein, to field strains, with respect to laboratory strains. From all findings, the coupling of LC₅₀, RR values and-related enzymes may recognize a reliable tool to assess S. littoralis resistance. Moreover, bioinsecticides and IGR.s were very effective to control leafworm in cotton fields.