Plant secondary metabolites (PSMs) strongly influence diet selection by mammalian herbivores. Concentrations of PSMs vary within and among plant species, and across landscapes. Therefore, local adaptations may cause different populations of herbivores to differ in their ability to tolerate PSMs. Here, we tested the food intake responses of three populations of a marsupial folivore, the common brushtail possum (Trichosurus vulpecula Kerr), from different latitudes and habitat types, to four types of PSMs. We found clear variation in the responses of northern and southern Australian possums to PSMs. Brushtail possums from southern Australia showed marked decreases in food intake in response to all four PSMs, while the two populations from northern Australia were not as sensitive and their responses did not differ from one another. These results were unexpected, based on our understanding of the experiences of these populations with PSMs in the wild. Our results suggest that geographically separated populations of possums may have evolved differing abilities to cope with PSMs, as a result of local adaptation to their natural environments. Our results provide the basis for future studies to investigate the mechanisms by which populations of mammalian species differ in their ability to tolerate PSMs.