Soybean plants are subjected to invasion by many insect pests. The cotton leafworm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae), is one of the most important pests that infect soybean plants causing a large loss in yield. The extensive use of conventional insecticides caused adverse impacts on the environment and natural enemies, besides the formation of resistance against these compounds. The present study aimed to evaluate the insecticidal activity of the efficacy of chemically mixed compound and its comparison with its active ingredients alone against the larvae of S. littoralis, and its predators in two growing seasons, 2020 and 2021. The field application revealed that the commercial mixture Folliam Felixi^® (Thiamethoxam + Chlorantraniliprole) significantly reduced the larval population of S. littoralis compared to Niloxam^® (Thiamethoxam), Coragen^® (Chlorantraniliprole), and the untreated area, through both growing seasons. The tested compounds showed no significant toxicity against the individuals of ladybird, Coccinella sp., and lacewing, Chrysoperla carnea, through both growing seasons. All tested compounds can be used successfully as a component of integrated pest management of cotton leafworm in Egypt.