Optimal digestion theory has been used to model expected changes in gut structure and function to maintain maximal digestive efficiency (DE) under changing food supply. For instance, DE typically decreases with increasing amounts of indigestible fiber in the diet. However, animals can remodel the gut, often displaying larger and longer GI tracts when on high fiber diets to maintain nutrient uptake as non-digestible materials slowly travel down the gut and encounter greater absorptive surface area. A detailed understanding of how physiological processes across levels of biological organization optimize function remains one of the “Grand Challenges” in animal physiology. Here, we studied three closely related rodent species with different feeding strategies, Microtus montanus (herbivore), Peromyscus leucopus (omnivore), and Onychomys torridus (insectivore). We fed individuals four different diets varying in fiber and protein content for five weeks. We observed plastic responses in small intestinal length, cecal mass, and activities of digestive enzymes, though each species exhibited unique increases and decreases in each function. Dry matter digestibility (DMD) and fiber digestibility (FD) also varied across species and as an effect of diet. Finally, we conducted path analysis to integrate our data and understand what physiological changes underly the variability in DMD and FD. Path analysis supported our idea that fiber is a main driver of plasticity followed by internal cellular processes. These data will enhance our understanding of optimal digestion theory and identify physiological changes that are most important for maximizing digestive performance.