In some governorates of Egypt, the African migratory locust L. migratoria migratorioides is in a gregarious phase. Swarm development was successfully prevented by biological control agents. In this work, the two entomopathogenic nematode species, Steinernema sp. (SII)and Heterorhabditis bacteriophora (HP88) were investigated as natural enemies against the fifth nymph and adult African locusts at various concentrations (300, 600, 900, 1200, and 1500 Infected juveniles/100 g. soil). To ascertain fatal activity at 25 °C, the nematode-inoculated sand method was used. The two nematode species were semi-field administered against fifth nymphs and adult stages at (25 ± 2 °C) and 55–60% relative humidity with concentrations (3000, 6000, 9000, 12000, and 15000 Infected juveniles/kg. soil). Protease, amylase, invertase, and trehalase levels in the digestive enzymes of both fifth nymphs and adults fed with LC₅₀ of both nematodes significantly decreased, but lipase and chitinase levels significantly increased. Adult locusts treated with the LC₅₀ of S. sp. SII had basophilic epithelial cells, severe lumen hemorrhage, and highly aberrant proliferating cytoplasm, whereas the LC₅₀ of H. bacteriophora HP88 displayed necrosis in an epithelial cell with vacuoles, loss of nucleus, and loss of goblet cells.