The purpose of current study was to enhance the nutritional value of cakes by substituting wheat flour by pumpkin fruit and its seeds as a source of protein, phenolics and flavonoids. Cakes were made by substituting wheat flour with a constant percentage of fresh pumpkin fruit (10% as dry weight) or replacement wheat flour with fresh pumpkin fruit using the same previous percentage and different levels of whole pumpkin seeds (10, 20, 30 and 40%). The different kinds of cakes were subjected for nutritional and sensory evaluation. Effect of feeding with cakes enhanced with pumpkin fruit and its seeds on serum biochemical analysis and histological examination of pancreas for alloxan-induced diabetic male rats after three months treatment was also assessed. Results estimated that cakes containing both fresh pumpkin fruit and whole pumpkin seeds showed significantly increased (P<0.05) in protein, fiber, ash, phenolics and flavonoids as well as this increase was associated with the level of substituting by whole pumpkin seeds compared to control cakes. Sensory quality revealed that cakes containing fresh pumpkin fruit and 40% whole pumpkin seeds were the most acceptable comparing with control cakes. Data showed that glucose, triglycerides (TG), cholesterol (TC) and low-density lipoprotein (LDL) levels for diabetic rats which fed on cakes enhanced with fresh pumpkin fruit or cakes containing both fresh pumpkin fruit and different levels of whole pumpkin seeds significantly decreased (P<0.05) in comparison with diabetic rats, whereas insulin and high-density lipoprotein levels were significantly higher (P<0.05) than diabetic rats. Findings revealed that a significant improve (P<0.05) in kidney and liver functions of diabetic rats treated with cakes enhanced with pumpkin (fruit or fruit and its seeds) compared to rats with diabetes. Histological analysis also clarified marked improvement in pancreatic tissues of diabetic rats treated with cakes enhanced with pumpkin (fruit and its seeds) comparing to diabetic rats and these findings are consistent with previous results mentioned above. The best improvement of different parameters was found in diabetic rats consumed cakes containing 40% whole pumpkin seeds and 10% pumpkin fruit as compared with diabetic rats where parameters reached to nearly normal values. In addition, these cakes contain the highest values of protein, fiber, phenolics and flavonoids, and the lowest levels from fat and calories comparing to control cakes. Therefore, it can be concluded that cakes prepared from pumpkin (fruit or fruit and its seeds) which were produced by the lowest cost considered from functional foods where pumpkin and its seeds had beneficial effects on nutritional and biological parameters of cakes. According to results, these cakes could be beneficial in the prevention and treatment of diabetes. Also, pumpkin cakes might be useful for people suffering from hyperlipidemia, obesity and malnutrition. Thus, this will help to promote the use of pumpkin cakes and management problems related to nutrition in Egypt. So, this study recommends increasing the production of food products containing pumpkin (fruit or fruit and its seeds) and improving nutrition education of people about the importance of consuming food products made from pumpkin and its many benefits for preventing and treating diabetes as well as other diseases in different media.