The mutualistic interaction between scatter-hoarding rodents and their seed plants is highly complex yet poorly understood. Plants may benefit from the seed dispersal behavior of rodents, as long as seed consumption is minimized. In parallel, rodents may maximize foraging efficiency and cache high-quality resources for future consumption. Defensive compounds, such as tannins, are thought to be a major mechanism for plant control over rodent behavior. However, previous studies, using naturally occurring seeds, have not provided conclusive evidence supporting this hypothesis. Here, we test the importance of tannin concentrations on the scatter-hoarding behavior of rodents by using an artificial seed system. We combined feeding trials and field observations to examine the overall impact of seed tannin concentrations on rodent behavior and health. We found that rodents favored seeds with an intermediate amount of tannin (~5%) in the field. Meanwhile, in rodents that were fed a diet with different tannin content, only diets with high tannin content (25%, 15%, and 10%) caused a significant negative influence on rodent survival and health. Significant differences were not found among treatments with tannin levels of 0–5%. In contrast to many existing studies, our results clearly demonstrate that scatter-hoarding rodents prefer slightly ‘astringent’ food. In the co-evolutionary arms race between plants and animals, our results suggest that while tannins may play a significant role in reducing general predation levels by the faunal community, they have no precise control over the behavior of their mutualistic partner. Instead, the two partners appear to have reached an evolutionary point where both parties receive adequate benefits, with the year-to-year outcome being dependent on a wide range of factors beyond the control of either partner.