Cognitive dysfunction has been increasingly considered as a major comorbidity of diabetes mellitus, which can result in non-adherence to recommended therapies and higher risk of hypoglycemic events. Although the exact mechanisms underlying the relationship between markers of insulin homeostasis and cognitive decline in patients with diabetes are still not fully understood, several studies have recently showed that dietary and/or pharmacological interventions exert beneficial effects in terms of prevention and improvement of diabetes-related cognitive decline. Therefore, a better understanding of molecular mechanisms that account for the pathological loop between diabetes and neurological dysfunction would allow for better prevention strategies and more tailored therapies, especially in the elderly population.