Lactate, a signaling molecule and energy source, crosses membranes through monocarboxylate transporters (MCTs). MCT1 and MCT4 are potential cancer drug targets due to their role in metabolic reprogramming of cancer cells. Stilbenes, plant secondary metabolites found in several food sources, have anticancer effects, though their mechanisms of action are not well understood. This study links the anticancer activity of natural stilbenes to tumor cell lactate metabolism. The impact of resveratrol, pinostilbene, pterostilbene, rhapontigenin, and piceatannol on lactate transport is studied using a fluorescence resonance energy transfer (FRET)-based lactate sensor. The viability and migration of cells expressing MCT1 or MCT4 are also evaluated. Piceatannol inhibits MCT1 effectively at low micromolar concentrations, with less effect on MCT4. All stilbenes significantly reduce cell viability and migration. These findings indicate that both MCTs are stilbene targets, with piceatannol highlighted as a cost-effective, low-toxicity compound for studying MCTs in cancer, providing a new mechanism of action of the therapeutic and nutraceutical effects of natural polyphenols. This enriches the understanding of dietary polyphenols in cancer prevention and therapy.