As omnivores, short-tailed cane mice are opportunistic feeders that consume both plants and animals. They are locally abundant throughout their range and may have a significant influence on insect pest populations. As herbivores and granivores, they likely disperse the seeds of various plants throughout their geographic range. They are an important prey item for a wide variety of carnivorous animals. Short-tailed cane mice are host to numerous ectoparasites, including mites (Laelaps dearmasi), lice (Hoplopleura nesoryzomydis), fleas, ticks and chiggers (Atelepalme smarma). They are also host to various endoparasites including pinworms and trichomonad protozoa. Short-tailed cane mice are reservoirs for various diseases, such as Yersina pseudotuberculosis, Hantavarus and murine coronavirus, which may affect local wildlife and human populations.