The present work investigated the date palm (Phoenix dactylifera L.) pollen (DPP) extract’s activity to reduce testicular injury induced by cimetidine (CM) in male albino mice. Male Swiss albino mice were divided into four groups with 10 mice in each. The first group served as the untreated control. The second group was treated with 500 mg/kg of DPP extract, third group with 400 mg/kg of CM, and the fourth group with DPP extract before CM treatment. The experiment lasted for 6 weeks. A CBC demonstrated increased WBC and platelets counts in the group treated with CM, which decreased in the group treated with the DPP extract before CM. Additionally, CM administration resulted in reduction of the testes index and the total sperm count and their viability%, but increased mortality %, whereas, treatment with the DPP extract before CM showed reverse of previous parameters. Hormonal analysis revealed decreased testosterone and increased prolactin in the group treated with CM, but the group treated with the DPP extract before CM showed marked increase of testosterone and decrease of prolactin. Oxidative stress marker malondialdehyde (MDA) was increased after CM treatment but the anti-oxidant marker glutathione (GSH) was decreased that modified by DPP extract treatment. Sperm morphology exhibited abnormal heads and coiled tails after CM treatment. Administration of the DPP extraction treatment before CM showed marked improvement in sperm morphology. Teste histopathological examination after CM treatment revealed observed vacuolar degeneration, absence of most spermatogenic stages with a decrease in Johnson’s pathological score, decrease in area and volume of seminiferous tubules. Treatment with DPP extract before CM displayed reduction of the testicular histopathological damage, an increase in Johnson’s score, and the morphometrics of seminiferous tubules. Immunohistochemical analysis against cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (inos) revealed a marked increase in the seminiferous tubules in the group treated with CM, but a decrease in the last group that was treated with DPP extract before CM. It was concluded that DPP extract could reverse the testicular damage induced by CM administration.