Cypermethrin (CYP) is a synthetic pyrethroid. It crosses the blood-brain barrier in pests and creates neurotoxicity in the CNS. Hydroxytyrosol (HT) is considered a powerful natural antioxidant, it is found in olive leaf, olive pulp and olive oil. Hydroxytyrosol is the only phenol that is capable to pass the blood-brain barrier and permits it to involve free radicals throughout the CNS. We designed this study to explore the possible protective role of HT against the neurotoxic effect induced by CYP. Thirty male adult albino rats were divided into three groups. Control group; subdivided into: control, corn oil, HT groups, CYP treated and CYP, CYP+ HT treated group. Treatments were given by gavage for 14 days. The cerebrum tissue was prepared for histopathological examination and immunohistochemical detection of caspase 3 and GFAP. We also assessed the level of GAPA and ACH in the tissue and the oxidative enzymatic and the lipid perioxidation profile. We observed that the concomitant use of HT with the CYP diminished the signs of hyper excitability induced by the CYP which confirmed by significant decrease in the level of GABA in cerebrum tissue. HT counteracted the histopathological changes induced by CYP and significantly downregulated the caspase -3 and GFAP expression in cerebrum tissue. A rescue of the oxidative enzymatic activity, lipid peroxidation profiles was also evident in the CYP+HT-treated group. We concluded that HT exhibited substantial antioxidant and anti-apoptotic impacts on the cerebral cortex cytomorphological alterations and apoptosis produced by CYP in cerebrum tissue.