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Natural bioactive compounds may be used in obese patients because of their ability to impact on various key mechanisms involved in the complex pathophysiological mechanisms of such condition. The aim of this study was to investigate the effect of a <i>Mangifera indica</i> L. leaf extract (MLE) on adipogenic differentiation of murine preadipocyte cells. 3T3-L1 cells were treated during their differentiation with various concentrations of (<i>Mangifera indica</i> L.) leaves extract (MLE) (750, 380, 150, 75 and 35 &#956;g) in order to assess their lipid content, adiponectin production, expression profile of genes involved in lipid metabolism, oxidative stress and inflammation. Our results showed that MLE was particularly enriched in polyphenols (46.30 &#177; 0.083 mg/g) and that pharmacological treatment of cells resulted in a significant increase of adiponectin levels and reduction of intracellular lipid content. Consistently with these results, MLE resulted in a significant decrease of the expression of genes involved in lipid metabolism (FAS, PPARG, DGAT1, DGAT2, and SCD-1). In conclusion, our results suggest that MLE may represent a possible pharmacological tool for obese or metabolic syndrome patients.