The search and discovery of new natural products with antifeedant and larvicidal potentials to mitigate harmful insects are scientific pressing issues in the modern agriculture. In this paper, the antifeedant and larvicidal potentials of 69 fungal isolates were screened against the Egyptian cotton leafworm Spodoptera littoralis. A total of 17 isolates showed the insecticidal potentials with three promising isolates. These strains were Aspergillus sydowii, Lasiodiplodia theobromae, and Aspergillus flavus isolated from Ricinus communis (bark), Terminalia arjuna (Bark), and Psidium guajava (twigs), respectively. The effect of gamma irradiation on the antifeedant and larvicidal activities of the three strains was investigated. Exposure of the fungal spores to 1000 Gy of gamma rays significantly intensified both the antifeedant and larvicidal potentials. To identify compounds responsible for these activities, extracts of the three strains were fractionated by thin layer chromatography. The nature of the separated compounds namely, Penitrem A, 1, 3, 5, 8- tetramethyl- 4, 6-diethyl- 7- [2- (methoxycarbonyl)ethyl] porphyrin (from A. sydowii), Penitrem A, 2, 7, 12, 17-Tetramethyl-3, 5:8, 10:13, 15:18, 20-tetrakis (2,2-dimethylpropano) porphyrin (from A. flavus), N,N-Diethyl-3-nitrobenzamide, and Diisooctyl-phthalate (from L. theobromae) were studied by GC-MS analysis. These findings recommend endophytic fungi as promising sources of novel natural compounds to mitigate harmful insects.