In this study, mustard and neem oils trad name saif oil (0.03% EC) were tested for their insecticidal activity against 2^nd and 4^th instar larvae of the cotton leafworm, Spodoptera littoralis. Also, the biochemical changes were evaluated to compare the physiological effects between the two tested oils. Toxicity results revealed that mustard oil has low toxicity versus the neem oil with LC₅₀ values of 7.99 and 20.30 when tested against 2^nd and 4^th larval instars, respectively. The toxicity index were 0.0024% and 0.0014 against 2^nd and 4^th instar larvae, respectively. A similar trend was recorded for both neem and mustard oils in the biochemical changes of protein and transaminase enzymes activities [aspartate aminotransferase (AST), alanine aminotransferase (ALT)] which decrease in both tested 2^nd and 4^th instar larvae  at all times intervals (1, 3, 5 and 7 days). In addition, the fluctuated effects were shown on lipids levels and amylase, invertase and trehalase activities.