Cellular senescence is a limiting factor in the proliferative expansion and quality of adult mesenchymal stem cells, often making them unviable in regenerative clinical practice. In vitro supplementation by antioxidant food extract of senescent mesenchymal stem cells could reverse these undesirable characteristics. To evaluate this hypothesis, senescent adipocyte-mesenchymal cells (ASCs) obtained from human lipoaspirates were exposed at different concentrations of hydro-alcoholic guaraná (Paullinia cupana) extract for 72 h. After the incubation, we performed a proliferative assay. Oxidative stress indicators and antioxidant enzymes (biochemical activity and gene expression by qRT-PCR analysis) in these senescent cells were also evaluated. In senescent cells exposed to guaraná at 5 mg/g concentration increased cellular proliferation occurred compared to untreated senescent cells (79.1 ± 15.7%). Concomitantly, a decrease in several oxidative stress indicators was observed in senescent cells treated with guaraná. A genomic effect of guaraná exposure was observed when the modulation of antioxidant enzymes genes was analyzed. The results described here suggest that the food extract supplementation could reverse the initial senescence processes in ASCs. These results have potential application in regenerative medicine.