We are witnessing an unprecedented rise in obesity and Type 2 diabetes. Until recently, study of the relation between metabolic dysregulation and higher brain function was limited. This paper summarizes the findings of a Spark workshop that focussed on the impact of obesity and diabetes on mood and cognition. Disturbances in peripheral glucose regulation are associated with cognitive impairment and depressed mood, especially in older adults. Multiple mechanisms and mediators underlie this association including insulin, glucose, neurotropic factors, glucocorticoids, inflammatory agents and reactive oxygen species. Importantly, prevention and even reversal of diabetes and obesity related cognitive impairment and depressive mood can be brought about by lifestyle modification. In particular, increasing physical fitness and moderating/changing food intake will have beneficial effects. Prevention of obesity and hyperglycemia by adopting a healthy lifestyle will contribute to the maintenance of functional integrity and mental health later in life.