A semi-field experiment was designed in order to assess the insecticidal activity of three new ryanodine receptor activators against the cotton leafworm, Spodoptera littoralis (Boisd.) during 2016 cabbage growing season. Second and forth instar larvae were offered treated cabbage leaves treated with the recommended dose of the tested compounds at 24-h, 48-h, 72-h, five days, seven days and nine days post spray. Results revealed that general pattern was observed for the formulations, where the toxicity is increased with increasing the time lapsed after treatment. Absolute mortality percentage was obtained at 72-h post exposure for all tested compounds in both 2^nd and 4^th instar larvae. In addition, results revealed that the detoxification enzymes activity increased compared to control. In conclusion, the ryanodine receptor activators represent a novel mode of insecticide action, have the most favorable toxicological and ecotoxicological profiles, these profile make this chemicals useful tool in IPM of S. littoralis, however, the resistance risk of cotton leafworm on these insecticides should not be overlook