Emerging evidence demonstrates that insulin has a modulating effect on metabolic and cognitive function in the brain, highlighting the potential role of aberrant brain insulin signaling in the pathogenesis of various neuropsychiatric illnesses. Neuroimaging paradigms using intranasal insulin (INI) as a pharmacological challenge have allowed us to study the effects of insulin in the human brain. In this scoping review, we conducted a systematic database search to identify relevant research studies that employed an INI-based neuroimaging assay of brain insulin signaling. Thirty-six studies met inclusion criteria for this review. INI was found to significantly modulate activity and cerebral blood flow in brain regions related to homeostatic/hedonic control of food intake, as well as cognition. This review highlights the putative role of insulin signaling in the brain and the potential therapeutic value of INI in patients with mental health, addiction, and co-morbid metabolic disorders.