In a trial to explore new alternatives to chemical insecticides whose negative side effects on humans and the environment are a serious concern, natural alternatives are being addressed to discover new, cost-effective, and environmentally friendly compounds. Therefore, the present study aimed to evaluate the toxicity and biochemical effects of Calotropis procera solvent leaf extracts (acetone, ethanol and hexane) against the 2^nd and 4^th instar larvae of Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae). The acetone extract was more toxic than ethanol and hexane extracts in both the 2^nd and 4^th instar larvae with LC₅₀ values:  5.733, 7.96 and 11.18% for 2^nd instar larvae and 7.507, 8.44 and 11.827% for 4^th instar larvae, respectively after 48h. of feeding on treated leaves, it was observed that 2^nd instar larvae were more sensitive than 4^th instar larvae for all extracts. The biochemical effects on S. littoralis 2^nd and 4^th instar larvae were determined using the LC₅₀ of each extract. All extracts exhibited decreasing activities for all determined enzymes: Aspartate Transaminase (AST), Alanine Transaminase (ALT), Acetylcholineesterase (AChE), Glutathione S-Transferase (GST) and total protein in both 2^nd and 4^th instar larvae. The results showed that the overall effects of C. procera leaf extracts on some biochemical components in S. littoralis larvae can facilitate the development of natural products as insecticides that can be employed in integrated pest management strategies. Keywords: Calotropis procera, Spodoptera littoralis, toxicity, enzyme activities and integrated pest management.