Assessing the effect of dietary ingredients on lipogenesis and glucose uptake in adipocytes may clarify the risk/benefit of recommending to individuals with obesity and insulin resistance. Grape powder extracted polyphenols (GPEP) modulate inflammation in human adipocytes. We hypothesized that GPEP increase intracellular fat accumulation and glucose uptake during differentiation of 3T3‐F442A preadipocytes. Total polyphenols were extracted and measured based on gallic acid equivalents (GAE). There were 2167 mg of GAE of polyphenols in 100 g of grape powder (GP). 3T3‐F442A cells were incubated with GPEP from 125 – 500 µg GP/mL of media until day 8 of differentiation when the cells were collected for different assays. Adipo‐Red assay and Oil Red O staining showed that GPEP induced, in a dose‐dependent manner, an increase in intracellular triglyceride content of adipocytes. Concomitantly, GPEP increased, in a dose‐dependent manner, glucose uptake by 3T3‐F442A cells. No changes in cell viability were measured by Trypan blue staining, suggesting that these effects were independent of cytotoxicity. Western‐blot showed that GPEP upregulated total and membrane protein level of GLUT4 in 3T3‐F442A adipocytes. Ly294002 (10 µmol/L), a phosphatidyl‐inositol 3 kinase (PI3K) inhibitor, reversed the effects of GPEP on cellular lipid content. Real‐time qPCR showed that GPEP increased mRNA expression of fatty acid synthase, lipoprotein lipase, and adiponectin, while it decreased mRNA expression of leptin and insig‐1. Our results indicate that GPEP may induce adipocyte differentiation via upregulation of GLUT4, PI3K and adipogenic genes.