Zinc oxide nanoparticles, have garnered a lot of attention due to their rapidly growing uses in several industries. The aim was to evaluate the impact of ZnONPs on rat cerebellar tissue and the possible neuroprotective function of fucoidan and selenium. fifty adult albino rats were separated into five groups; group I (control); Ia received no treatment, Ib received (IP) injections of normal saline (0.9%), Ic were given filtered water, Group II were given 400 mg/kg b.wt. of ZnONPs intraperitoneally for 1 month, group III were given ZnONPs injections plus selenium orally at a dosage of 0.5 mg/kg b.wt./day for 1 month, group IV were given ZnONPs injections plus an intraperitoneal injection of fucoidan at a daily dose of 80 mg/kg body weight for 1 month and group V were given ZnONPs injections plus selenium and fucoidan for 1 month. The cerebellar cortex specimens were prepared for histological, biochemical, and immunohistochemical investigation. Evaluations were conducted using both morphometric and statistical methods. ZnONPs significantly raised MDA levels, while significantly lowering SOD and GSH levels in comparison to control group. Histologically, Purkinje cells were destroyed. While the average area percent of glial fibrillary acidic protein (GFAP) and caspase-3-positive cells' immunostain substantially increased, the optical density of calcium binding protein (calbindin) immunopositive cells dramatically reduced. In comparison to the ZnONPs group, both selenium and fucoidan treatments significantly reduced MDA levels and significantly improve SOD and GSH levels. So administration of selenium and fucoidan significantly ameliorated the cerebellar alterations induced by ZnONPs in rats.