The present study aimed to verifies the effect of four strains of entomopathogenic nematodes, Heterorhabditis bacteriophora (HP88), Steinernema carpocapsae (S.C), Steinernema scapterisci (S.S), Steinernema glaseri (S. g) against the last larval instar of the greater wax moth G. mellonella. The biochemical alterations due to nematodes infection were conducted after four exposure times 6, 12, 24 and 48hrs and by 20, 50 and 100 infective juveniles (IJs) concentrations. Results demonstrate that all treatments provoke dysfunction in carbohydrate hydrolyzing enzymes (amylase, Trehalase and Invertase) and α- and β- esterase enzymes. At 20 (IJs) all treatments cause a significant reduction in the activity of amylase, in contrary both S. scapterisi (S.S) and S.glaseri (S. g) caused a non-significant increase at 6h after treatments. Significant elevation in the activity of amylase enzyme after 6h recorded by 50 IJs.  The maximum level was reported after treatment with H. bacteriophora (HP88) (510.50±3.33 µg glucose/g. b. wt.) with a change percentage of 47.24% compared to control. Meanwhile, H. bacteriophora (HP88) strain caused a significant reduction in the activity of the enzyme (235.70±2.58 and 175.60±6.53 µg glucose/g. b. wt.) with a percentage of change, -59.86% and -68.67% after 12 and 48h, respectively compared with control. Also, HP88 treatment exhibited inhibition in trehalase activity at 100 ( IJ) as well as, the measured values of the enzyme are (1431.08±3.33, 743.14±4.89 and 467.17±3.08 µg glucose/g. b. wt.) with inhibition percentage of -42.08, -41.00 and -52.50% after 6, 24 and 48hrs, respectively after treatments. The invertase enzyme activity showed a significant decrease at 20 (IJ) after 6 and 12 hrs and reversed action recoded, a significant increase after 24hrs with all strains as compared to control. At 50(IJ) The treatment with (S. g) caused an initial increase in α-esterase activity then, a significant decrease in the enzyme activity recorded and gave (270.10±1.85 and 234.00±2.21 μg β-naphthol /g. b. wt.) with percentages of -30.00 and -44.00 % after 24 and 48hrs, respectively of treatment compared with control. The treatment with (S.C) had a significant decrease in β esterase activity and reached (189.90±2.93μg β-naphthol /g. b. wt.) with percentage of -46.60% after 12hrs from treatment. On the contrary there was increase in β esterase enzyme recorded the highest values (442.20±2.25 and 523.40±2.61μg β-naphthol /g. b. wt.)), respectively after 24 and 48hrs of treatments.