Alzheimer's disease is the most common form of dementia, and its prevalence is increasing worldwide. Therefore, understanding the disease's pathogenesis is of utmost importance. To this end, we performed untargeted metabolomic assays and targeted qPCR on postmortem visual cortex tissue from subjects diagnosed as cognitively normal control (Ctrl), mildly cognitively impaired (MCI), or with Alzheimer’s disease (AD). The subjects were closely split by sex, had comparable post-mortem intervals, were all Caucasian, and none were diagnosed with metabolic disease. The metabolomic assay revealed an upregulation in multiple metabolites in the glycogen synthesis and glycolysis pathways in the AD subjects. To further probe these findings, we generated heat maps and found a reduction in acetyl-CoA in the AD group. When evaluating the mRNA expression of key GLUTs in the CNS, we found a decrease in the AD group compared to the others. The AD groups also had a reduction in mRNA expression of key rate-limiting enzymes in the glycolytic pathway. Furthermore, we compared key energy metabolites and found that NADH, NAD+, and FAD were all reduced in the AD group compared to the MCI group. Lastly, we evaluated the mRNA expression of key proteins regulating insulin signaling. There was an increase in the mRNA expression of protein tyrosine phosphatase 1B and Src homology 2 domain-containing protein tyrosine phosphatases, and a decrease in the insulin degradation enzyme. In conclusion, the visual cortex tissue of the AD subjects demonstrates a shift in the metabolites involved in glucose metabolism and energy availability, a reduction in the mRNA expression of enzymes that break down glucose, and a shift in mRNA expression of enzymes that regulate insulin signaling in a way that promotes insulin resistance. Our results corroborate other laboratory’s findings and suggest that improving metabolic status may be a promising therapeutic strategy for treating AD.