Toxic-induced cerebellar syndrome (TOICS) poses substantial neurological challenges, given its diverse causes and complex manifestations. Gold nanoparticles (AuNPs) have gained significant attention owing to enhanced biocompatibility for therapeutic interventions. We aimed to investigate the impacts of AuNPs on cerebellar cytomolecular, immunohistochemical and ultrastructural alterations in the context of phenytoin-experimentally induced TOICS. Thirty male albino rats were assigned randomly to three equal groups; control, phenytoin (PHT) and PHT+ AuNPs groups. Cerebellar sections were examined histopathologically, ultra-structurally and immunohistochemically for GFAP and p-Tau. Cerebellar tissues were evaluated for TNF-α, IL-1β, MDA, CAT, SOD and CREB mRNA. Our data confirmed observable amelioration of histopathological and ultrastructural cerebellar alterations of Purkinje and granule cells after AuNPs cotreatment. Histomorphometric measures revealed AuNPs-induced significant downregulation of p-Tau and GFAP immune-expression. Concurrently, TNF-α, IL-1β, MDA were significantly quenched in cerebellar tissues after AuNPs cotreatment, on contrary to notable restoration of CAT, SOD and CREB mRNA levels. These outcomes confirm that AuNPs hold promise as a therapeutic strategy for TOICS, warranting further exploration of their mechanisms and clinical applications in cerebellar disorders.