The invention encompasses compositions and methods for effectively treating and/or preventing diabetes and/or obesity. This is accomplished by totally addressing the multiple mechanisms that lead to such conditions. The invention includes compositions comprising a combination of agents that effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that lead to diabetes and obesity. The inventive compositions used for administration to human and other mammalian subjects comprise (1) at least one agent capable of modulating expression and/or activity of one or more of peroxisome activated protein receptor gamma (PPAR-γ), CAAT/enhancer binding protein-α (C/EBPα) and Sterol Regulatory Element-Binding Protein (SREBP-1); (2) at least one agent capable of activating Wnt/β-catenin pathway; (3) at least one agent capable of activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway; (4) at least one agent that inhibits the activity of pro-oxidants including reactive nitrogen species and reactive oxygen species (ROS); (5) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2); (6) at least one agent capable of enhancing glucose transporter (GLUT4) and/or inhibiting glucose transporter GLUT2; (7) at least one agent that induces the expression of and/or activates adiponectin and (8) at least one agent that induces the expression of and/or activates sirtuin (SIRT1). The active agents for use herein are natural materials such as phytonutrients, vitamins and minerals. Compositions with combinations of such natural agents have the ability to prevent, reduce or treat diabetes and obesity by (a) clearing glucose and fatty acids from blood, (b) reducing the number of adipose cells and fat storage, (c) interfering with fat, glucose, and cholesterol biosynthesis, and (d) promoting fat