Background: Disruptive cholinergic neurotransmission and abnormal cognitive functions were the characteristics of Alzheimer's disease leading to abnormal brain–liver inflammatory responses. Oxidative stress was prominent in Alzheimer's disease-related neurodegeneration leading to inflammatory communication through altered cytokines between the brain and peripheral organs, mainly the liver. Objectives: Current study would demonstrate the healthier effect of N-acetyl cysteine and rutin against AD in rats. Materials and Methods: Experimental Wistar rats have been grouped appropriately for the administration of scopolamine and treatment using a combination of N-acetyl cysteine and rutin for 10 weeks. Results: In our study, scopolamine (2 mg/kg b.w.i.p.) administered Alzheimer's disease model in Wistar rats showed abnormality in behavioural changes (Morris water maze test), pro-inflammatory cytokines, decreased activities of enzymatic antioxidants, decreased reduced glutathione content, elevated brain oxidative stress markers, increased amyloid-beta, elevated acetylcholinesterase, elevated butyrl cholinesterase, increased phosphorylated tau protein, increased GSK-3β, BDNF, altered expressions of β-secretase, NADPH oxidase 2, and Nrf2 genes in brain, and augmented oxidative stress in liver affecting brain–liver axis. Oxidative stress in the liver was evident through decreased activities of enzymatic antioxidants, decreased glutathione content, and elevated liver oxidative stress markers. Conclusion: Treatment with N-acetyl cysteine with rutin showed protective efficacy by modulating the pathways related to Nrf2, NOX-2, and BACE1 genes in combating these abnormalities in rats. Modulation in the gene expressions in the brain tissue showed direct evidence of the drug's neuroprotective efficacy for future therapeutic strategies in scopolamine-induced Alzheimer's disease.