This study investigated the effect of co-culture soy milk against hyperglycemia and hypercholesterolemia on Sprague Dawley rats. Soy milk fermented by co-culture (L. acidophilus and L. casei) and analyzed for certain physicochemical properties to compare it with non-fermented soy milk. Then bio-efficacy study was done designed as study I (Normal rats) study II (Hyperglycemic rats) and study III (Hypercholestrolemic rats). Serum lipid profile, glucose, insulin level, liver (AST, ALT, ALP), renal (creatinine, BUN) functioning and hematological (RBC, WBC) analyses were determined. The results showed that fermentation causes proteolysis and lipolysis that significantly enhances the acidity, ash contents and antioxidant potential of soy milk. Compared to non-fermented soy milk (NFSM) the co-culture fermented soy milk (CFSM) resulted in reduction of glucose level from 3.61 to 17.11% and inclining insulin level from 1.8 to 8.3% in diabetic rats. It was most effective in lowering cholesterol level from 2.62 to 13.51%, the LDL reduction from 6 to 12.47% and elevation of HDL from 2.78 to 9.52% in hypercholesterolemic rats. The safety test on liver, kidney and blood biochemistry suggested it as a safe and non-toxic product. The current research proposed that soymilk fermented by L. acidophilus and L. casei has a valuable effect against hyperglycemia and hypercholesterolemia in comparison to non- fermented soy milk in managing diabetes complications and cardio vascular diseases.