Obesity is an established risk factor for metabolic disease. This study explores the functional complementation of anti-adipogenic phytonutrients for obesity prevention and management. Nine phytonutrients were selected based on their ability to affect the expression of one or more selected adipogenic biomarker proteins. The phytonutrients include berberine, luteolin, resveratrol, fisetin, quercetin, fucoidan, epigallocatechin gallate, hesperidin, and curcumin. The selected adipogenic biomarker proteins include PPARɣ, SREBP1c, FASN, PLIN1, FABP4, and β-catenin. Individually, phytonutrients had variable effects on the expression level of selected adipogenic biomarker proteins. Collectively, the functional complementation of nine phytonutrients suppressed de novo fatty acid biosynthesis via the negative regulation of PPARɣ, FASN, PLIN1, and FABP4 expression; activated glycolysis via the positive regulation of SREBP1c expression; and preserved cell-cell adhesion via the inhibition of β-catenin degradation. In primary human subcutaneous preadipocytes, the composition of nine phytonutrients had more potent and longer lasting anti-adipogenic effects compared to individual phytonutrients. In a diet-induced obesity murine model, the composition of nine phytonutrients improved glucose tolerance and reduced weight gain, liver steatosis, visceral adiposity, circulating triglycerides, low-density lipoprotein cholesterol, and inflammatory cytokines and chemokines. The functional complementation of anti-adipogenic phytonutrients provides an effective approach toward engineering novel therapeutics for the prevention and management of obesity and metabolic syndrome.Keywords:adipogenesis; functional complementation; metabolic syndrome; nutraceuticals; nutrition intervention; obesity; phytonutrients; weight management.