We employed a rodent model to typify histomorphological changes connected to dementia-like symptoms and co-morbid insulin resistance; we examined neuronal density and morphological changes in the neurons of the prefrontal cortex (PFC); evaluated amyloid beta (Aβ) deposits and probed the association between phosphatidylinositol 3-kinase (PI3K), serine/threonin protein kinase (AKT) and glycogen synthase kinase 3β (GSK3β) activity and oral curcumin regimen. 36 adult Wistar rats were randomized into six groups (n=6) and treated with: (olive oil) control group; (curcumin) for positive control; High Fat Diet (HFD) and three doses of Streptozotocin (STZ) for diabetic; (HFD, three doses of STZ and concurrent curcumin) preventive; (pre-treatment with curcumin, followed by HFD and three doses of STZ) protective group; (HFD, three doses of STZ followed by curcumin) for therapeutic group. Cortical sections were stained for histological and histochemical investigations. ELISA was used for quantifying PI3K, AKT and GSK3β activity. Data was analyzed using one-way ANOVA and Turkey’s post hoc test. p<0.05 was considered significant. Findings indicate that oral curcumin significantly reduced blood glucose and insulin resistance. Insulin resistance was associated with cyto-architectural deficits observed in the PFC, while curcuminn ameliorated observed changes; furthermore, Oral curcumin reduced Aβ deposits in the PFC of the model. The impaired activity of PI3K, AKT and GSK-3β of the model was ameliorated by oral curcumin. The study concluded that oral curcumin showed ameliorative potentials on the PFC of adult male Wistar rats against neuronal death associated with dementia and insulin resistance.