Background: Azadirachta indica (Neem) has been used traditionally for many centuries. Some impressive therapeutic qualities have been discovered. Aim: Our study aims to investigate in vivo antitumor, and antioxidant activities of Ethanolic Neem Leaf Extract (ENLE) and its fraction Nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica). Also, to study the side effects of Ethanolic Neem leaf Extract and Nimbolide fraction on different organs (Liver/ Kidney). Materials & Methods: We assessed the effect of nimbolide and Ethanolic Neem Leaves Extract (ENLE) on life span prolongation and on the levels of malondialdehyde (MDA), nitric oxide (NO), Catalase, glutathione peroxidase (GPx), Caspase-3, and Cytochrome c. Also, our study estimated their effect on Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Protein (T.P), Albumin (Alb), bilirubin, urea and creatinine. Results: Ethanolic neem leaves extract and nimbolide showed great increase in life span. Also, they showed a significant decrease in malondialdehyde and nitric oxide and an increase in catalase, glutathione peroxidase, caspase-3 activities, and cytochrome c concentration. Hence, it may be possible that Nimbolide and ENLE decrease lipid peroxidation level due to their antioxidant effect and enhance apoptosis process. Neem leaves extract and nimbolide showed no side effects on liver and kidney. Also, they showed a significant protection for both liver and kidney histopathologically.