Investigation of green pesticides is the most important method to maintain sustainable agriculture and avoid health and environmental hazards resulting from the excessive use of chemical pesticides against controlling cotton leafworm Spodoptera littoralis. Therefore, the present study evaluated the toxic effects of four different pomegranate peel extracts against 2^nd and 4^th instar larvae of cotton leafworm during different exposure periods (24, 48, 72 and 96 hours). Ethanolic pomegranate peel extract (EPPE) resulted in the highest toxic effect with LC₅₀ values (0.0014 and 0.0022 %) after 96hrs against 2^nd and 4^th instar larvae. While those values of Hexane (HPPE), Methanol (MPPE) and Acetone (APPE) pomegranate peel extracts were (0.0019 and 0.0042 %), (0.002 and 0.0043 %), (0.0022 and 0.0045 %), respectively. Pretreatment with LC₅₀ of the most potent extract (EPPE) after 48 hours of exposure resulted in biological changes represented by a significant decrease in the percentage of pupation (30.94% and 41.4%) of 2^nd and 4^th instar larvae, respectively, compared to the control (95% and 84.2%). EPPE treatment highly affected the sex ratio (number of emerged males was greater than females). EPPE treatment induced a highly significant decrease in total protein and soluble carbohydrate content in both the 2^nd and 4^th instar. The total lipid content increased weakly in the 2^nd instar but no significant difference in processing was recorded in the 4^th instar when compared to the control. The present study suggested using pomegranate peel extract in integrated pest management programs of S. littoralis especially against early larval instar.