Background: Stress became a global challenge that leads various chronic diseases especially neuro-degeneration diseases such as Alzheimer__ampersandsignrsquo;s disease. Polyphenolic compounds were reported to possess protective effects against the cellular stress and can be used in the management of stress associated chronic diseases. Objectives: Our current work is aimed to design a better model to induce Alzheimer__ampersandsignrsquo;s disease through Diabetes and to screen the protective effect of Citrus reticulata and Citrus sinensis against diabetes-associated Alzheimer__ampersandsignrsquo;s disease. Methods: A comparative study was carried out on Streptozotocin - Nicotinamide induced Diabetes and High fat diet-induced Diabetes. Various biochemical, behavioural and histological parameters are considered to evaluate the best model for the diabetes-induced Alzheimer__ampersandsignrsquo;s disease along with the protective effect of selected Citrus reticulata (Tangerine oil) and Citrus sinensis (Orange oil) against diabetes-associated memory deficits. Results: Results showed that the high-fat diet model succeeded to create diabetes-associated memory impairment compared to Streptozotocin - Nicotinamide model. Detailed investigation of all the selected parameters of Tangerine and Orange oil groups by comparing with a standard group showed statistically significant (p__ampersandsigngt;0.0001) improvement in the Alzheimer__ampersandsignrsquo;s disease. Conclusion: To conclude, all the biochemical, behavioural and histological data declared that the high-fat diet model is the best model for studying diabetes-associated memory deficits in animals. It is also apparent that the oil of Citrus sinensis is more potent than Citrus reticulata to give protection against oxidative stress and subsequent improvement of memory and other physiological parameters. The antioxidant property of the oils may be responsible for the reported activity.