Recently, scientists searched for safe alternatives to synthetic insecticides to manage the cotton leafworm Spodoptera littoralis. Of these alternatives are microbial-based insecticides. These compounds are known for their unique larvicidal activity, especially against Lepidopterous insects. In this regard, the present investigation was carried out to evaluate the latent and histopathological influence of Bacillus thuringiensis var. kurstaki (Btk) and Spodoptera littoralis nuclear polyhedrosis virus (SpliNPV) either individually or in a mixture against the adult female of S. littoralis. The LC₅₀ values of the tested entomopathogens were determined. The impact of median lethal concentrations of tested entomopathogens on adult longevity, fecundity, and fertility was assayed after treating 2^nd instar larvae. In addition, the histological changes in female ovaries due to treatment were investigated. Results showed that the low LC₅₀ value showed that Btk+SpliNPV was the most hazardous against the 2^nd instar larvae, followed by SpliNPV and Btk. All tested entomopathogens did not cause high immediate larval mortality; however, larval mortality increased throughout the larval stage until pupation. There was also a significant reduction in fecundity and fertility of emerged females resulting from 2^nd instar larvae treatment. In addition, the treatment caused severe alterations in the histological structure of ovarioles. These findings support entomopathogens as a non-toxic alternative to conventional pesticides for controlling the cotton leafworm. Because of this, the population density of succeeding generations may decline since these organisms kill the treated larvae and have delayed effects that appear to reduce the eggs deposited and hatching. The results explain the reduced reproductive potential since these entomopathogens influence the female reproductive system when applied alone or as a mixture.