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Levels of obesity-linked non-insulin-dependent diabetes mellitus (NIDDM) and hypertension are highest among indigenous communities in North America. This is linked to changes in dietary pattern towards high calorie foods such as sugar, refined grain flour, and sweetened beverages. Therefore, a return to traditional dietary patterns may help to reduce these disease problems because of better balance of calories and beneficial nutrients. Further protective non-nutrient phenolic phytochemicals against NIDDM and hypertension are potentially high in these foods but less understood. In this study antidiabetic- and antihypertension-relevant potentials of phenolic phytochemicals were confirmed in select important traditional plant foods of indigenous communities such as pumpkin, beans, and maize using in vitro enzyme assays for -glucosidase, alpha-amylase, and angiotensin I-converting enzyme (ACE) inhibitory activities. In vitro inhibitory activities of these enzymes provide a strong biochemical rationale for further in vivo studies and dietary management strategy for NIDDM through the control of glucose absorption and reduction of associated hypertension. These enzyme inhibitory activities were further compared to total soluble phenolic content and antioxidant activity of the above-targeted plant foods. Pumpkin showed the best overall potential. Among the varieties of pumpkin extracts P5 (round orange) and P6 (spotted orange green) had high content of total phenolics and moderate antioxidant activity coupled to moderate to high alpha-glucosidase and ACE inhibitory activities. Therefore this phenolic antioxidant-enriched dietary strategy using specific traditional plant food combinations can generate a whole food profile that has the potential to reduce hyperglycemia-induced pathogenesis and also associated complications linked to cellular oxidation stress and hypertension.