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Accumulating evidence suggests that disrupted brain insulin signaling promotes the development and progression of Alzheimer's disease (AD), driving clinicians to target this circuitry. While both traditional and more modern antidiabetics show promise in combating insulin resistance, intranasal insulin appears to be the most efficient method of boosting brain insulin. Furthermore, intranasal delivery elegantly avoids adverse effects from peripheral insulin administration. However, there remain significant open questions regarding intranasal insulin's efficacy, safety, and potential as an adjunct or mono-therapy. Thus, this review aims to critically evaluate the present evidence and future potential of intranasal insulin as a meaningful treatment for AD.This article is part of the Special Issue entitled ‘Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.’Alzheimer's disease (AD) is hallmarked by impaired brain insulin signaling.Intranasal (IN) insulin reaches the brain in physiologically relevant levels.Findings indicate that IN insulin improves AD symptomology.Gender, genotype, and insulin formulation modify patient response.