This study investigates the in vitro and in vivo biological activities of mycogenic Zn nanoparticles synthesized by Aspergillus fumigatus (AFZN) as an effective neurological, antioxidant, antibacterial, antiviral, and anticancer agents besides mitigating the Al toxicity in albino mice. The spherical AFZN were 39nm in size and -23.6mV charge; these properties possessed the antioxidant, anticancer, antibacterial, antiviral, and anti-alzheimer activities. The in vitro findings revealed that AFZN (100 µg/mL) significantly inhibited 89% of DPPH radicals, 84% of the activity of AChE, and 85% of brain cancer cell lines besides pathogenic bacteria. The obtained ZnNPs reduced the severity of the lumpy skin disease virus (LSDV) by 84%. The antioxidant and neurological activity of ZnNPs in AlCl3-challenged mice were evaluated; therefore, 120 mice were allocated into six groups: control, three groups received ZnNPs concentrations (25, 50, and 75 mg/kg), AlCl3-challenged group, and AlCl3- challenged group and treated with ZnNPs (75 mg/kg). The dietary ZnNPs (75 mg/kg) significantly enhanced body weight gain, feed intake, and feed conversion ratio compared to the control and AlCl3-challenged group. The liver enzymes (AST and ALT), uric acid, total cholesterol, LDL, and MDA were at a high level in AlCl3- challenged groups, whereas ZnNPs (75 mg/kg) treatment enhanced the oxidative stability and immunity markers in the AlCl3-challenged group, where decreased MDA, and enhanced the activity of the enzymatic defence system (SOD, CAT, and GPx). Also, it downregulated the brain, liver, and renal proinflammatory (OCCU and MUC-1, IL-6, and IL-1β) and pro-cancerous (Bax and caspase-3) markers in the AlCl3-challenged group. The brain, liver, and kidney histology correlated with the results of biochemical parameters, where ZnNPs application recovered the tissue structure as control. It concluded that mycogenic ZnNPs can be used as an antioxidant and anti-alzheimer agent in the AlCl3-challenged group