Metabolic syndrome is the accompaniment of multiple risk factors for atherosclerotic cardiovascular disease and type 2 diabetes (T2D) including glucose intolerance, hypertension and dyslipidemia where obesity is the basic element at this syndrome. T2DM is a heterogeneous metabolic syndrome resulting from genomic-environment complex interaction. Pumpkin seeds and gum Arabic are two natural products with an obvious hypoglycemic role. Vildagliptin is a selective inhibitor of dipeptidylpeptidase-4 (DPP-IV), and a certified therapy for T2DM. This study has been destined to assess in vivo the hypoglycemic impact of pumpkin seeds and gum Arabic in compare with vildagliptin and their combination treatments. 70 male albino rats were randomly separated into seven groups of ten each: control non-diabetic, control non-treated diabetic, diabetic treated with pumpkin seed extract (300mg/kg/day), diabetic treated with gum Arabic (500mg/kg/day), diabetic treated with vildagliptin (10mg/kg/day), diabetic treated with a combination of pumpkin seed extract and vildagliptin, and diabetic treated with a combination of gum Arabic and vildagliptin.T2DM was stimulated by feeding rats on high fat-high fructose/sucrose diet regimen (HFHF/S) for 12 weeks. Biochemical assessment has revealed that pumpkin seed extract, gum Arabic and vildagliptin can alleviate the severity of hyperglycemia, insulin resistance, dyslipidemia and depress glucagon secretion