1 Pharmacology & Toxicology Department, Faculty of Pharmacy & Pharmaceutical Industries, Sinai University, El-Arish 45518, Egypt 2 Biological Sciences Department, College of Science & Arts, King Abdulaziz University, Rabigh 21911, Saudi Arabia 3 Laboratory of Transmissible Diseases and Biologically Active Substances, Faculty of Pharmacy, University of Monastir, Monastir 5019, Tunisia 4 Pharmacology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt 5 Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City 32897, Egypt 6 Histology and Cytology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt 7 Theriogenology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt 8 Department of Biology, College of Science, University of Jeddah, Jeddah 21493, Saudi Arabia 9 Pesticide Department, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt Abstract Aim: Chlorpyrifos (CPF) is a common organophosphorus insecticide. It is associated with negative consequences such as neurotoxicity and reproductive injury. This study aimed to observe the ability of olive leaf extract to attenuate chlorpyrifos toxicity, which induced neuro- and reproductive toxicity in male albino rats. Olive leaf extract (OLE) exhibits potent antioxidant and antiapoptotic properties. Methods: Twenty-two mature male rats were divided into four groups: control (saline), CPF (9 mg/kg), OLE (150 mg/kg), and CPF + OLE. Treatment was administered orally for 80 days. Results:The CPF significantly reduced serum sex hormones, sperm counts and motility, high oxidants (MDA), and depleted antioxidants (GSH, SOD, TAC) in the brain and testes homogenate; additionally, it decreased serum AChE and brain neurotransmitters, increased Bax, decreased Bcl-2, and boosted caspase-3 immune expression in neural and testicular cells. Immunological expression of Ki 67 in the cerebrum, cerebellum, choroid plexus, and hippocampus was reduced, and αSMA in testicular tissue also decreased. Histopathological findings were consistent with the above impacts. OLE co-administration significantly normalized all these abnormalities. OLE showed significant protection against neural and reproductive damage caused by CPF.