Zinc oxide nanoparticles (ZnO NPs) are the most used nanoparticles in the profitable arenas. Mureer (Senecio glaucus L. plant) (SP) is one of the natural plants in the deserts. Gallic acid (GA) deeds as an impotent antioxidant used in the treatment of various diseases. This study intended to gauge the lethal impacts of either single or dual treatments of zinc oxide nanoparticles (ZnO NPs) and mureer (Senecio glaucus L. plant) (SP) in neural tissue via scrutinizing the biochemical indices and histological examination to assess the convenient outcome of gallic acid (GA) against them for 30 days in rats with oral injection, and to ascertain the chemical constituents of SP, using Liquid Performance Mass Liquid Chromatography (HPLC-MS) method. Rats were alienated into eight groups: Control, GA (100 mg/kg), ZnO NPs (150 mg/kg), SP (400 mg/kg), GA+ZnO NPs (100,150 mg/kg), GA+SP (100,400 mg/kg), ZnO NPs+SP (150, 400 mg/kg), and GA+ZnO NPs+SP (100,150,400 mg/kg). Our results revealed that single or dual treatments of ZnO NPs and SP decreased the activity of acetylcholinesterase (AChE) and upraised the activity of lactate dehydrogenase (LDH), as well as the level of total lipids (TL) compared to the control group. Likewise, they prompted inflammation, neuronal degeneration, and cerebral hemorrhage. Our facts also revealed that the toxic effect of the dual group of ZnO NPs and SP was more than the effect of the single group. Contrariwise, our results estimated that GA amended neural injury. To sum up, this study presented that ZnO NPs and SP parade as neurotoxic agents; yet, GA acts as a neuroprotective agent.