Studies have suggested that total energy intake and diet composition affect lifespan and ageing. A high-fat diet induces oxidative stress and affects the development of diseases. In contrast, antioxidants are capable of reducing its harmful effects. Yerba mate beverages are an important source of antioxidants, but there is scarce knowledge about their effects on suppressing fat accumulation. Here, we investigated the compounds present in yerba mate extracts and assessed their effects on Drosophila melanogaster given a high cholesterol diet. LS-ESI-MS analysis showed the presence of matesaponins, phenolic compounds and methylxanthines in all of the examined extracts. In Drosophila, under extract treatment conditions, the mean lifespan was significantly extended from 38 to 43 days, there was an increase in the ability to support induced stress and decrease in lipid peroxidation products. Moreover, yerba mate extracts recovered the glutathione S-transferases (GST) activity and reduced the cholesterol level. Taken together, our results support that extracts can extend lifespan by reducing the detrimental effect of a high-fat diet in D. melanogaster, and this outcome can be associated with the compound content in the extracts. This study improves the understanding of natural interventions that reduce stress-induced oxidative damage, which is fundamental in promoting healthy ageing.