A complex mixture of organic contaminants and metals is associated with neuron-fertility disorders and studies have demonstrated that phenolic antioxidants from herbal origin, possesses a strong protective potential. This study aimed to investigate the protection of phenolic croton zambesicus (C-ZAMB) leaves against neuro-ovarian damage in rats exposed to chronic mixture of anthropogenic toxicants (EOMABRSL). The animals were divided into five groups (n = 10): Group I was given 0.5 ml of distilled water only; Group II received 0.5 ml of EOMABRSL for 98 days; Group III received 0.5 ml of EOMABRSL for 70 days and withdrew for 28 days; Group IV received 0.5 ml of EOMABRSL for 70 days +400 mg/kg phenolic C-ZAMB for 28 days; Group V received 400 mg/kg C-ZAMB only for 28 days via oral route. Both non-withdrawal and withdrawal EOMABRSL-exposed animals exhibited neuro-ovarian impairment by up-regulating neuronal 5 1 eco-nucleotidase (5 1 ENT), acetylcholinesterase (AChE), butrylcholinesterase (BuChE), synaptosomal monoamine oxidase-A (MAO-A) with altered cerebral antioxidants. Similarly, exposure to EOMABRSL for 98 and 70 days caused ovarian injury by amplifying the activity of 5 1 ENT with corresponding decline of fertility index, lactate dehydrogenase (LDH) and Δ5 17β-hydroxyl steroid dehydrogenase (Δ517β-HSD). EOMABRSL intoxication also increased the neuro-ovarian MDA content with reduced numbers of neonates. Phenolic antioxidants from C-ZAMB leaves identified by High Pressure Liquid Chromatography (HPLC) ameliorated the chronic EOMABRSL intoxication. The treatment also prevented ovarian lesions by depleting MDA content and improved antioxidant status. Thus, confirming its neuro-ovarian protection.