Isoflavones have been identified as potential anti-diabetic agents, but adverse side effects especially at high dosage has continued to plague their clinical uptake. We explore the benefits of individual and co-treatment of diabetic rodents with isoflavone-rich kudzu extract and chaga extract based on effect on glycemic control, regeneration of pancreatic β-cells (immunofluorescence staining assessment of pancreatic insulin and pancreatic and duodenal homeobox 1 (PDX-1) expression), cardiac function (including measurements of left ventricular hemodynamics, and arterial stiffness) and kidney function. Treatment of diabetic rodents with either isoflavone or chaga extract improved glycemic control, enhanced the co-expression of insulin and PDX-1, prevented cardiac hypertrophy, and ameliorated hypercellularity of the glomerulus, expansion of the mesangial matrix and deposition of collagen in kidney tissues. The use of both compounds combined did not provide additional benefits beyond that of each used singly. Further research focusing on exploring the optimal dosage of these combined therapies in experimental diabetes models is highly recommended. © 2024 The Author(s)