Monarch butterflies (Danaus plexippus) are frequently infected by a specialist protozoan parasite (Ophryocystis elektroscirrha). Feeding on milkweeds (Asclepias spp.) higher in toxic cardenolides as caterpillars increases resistance to the parasite. Here, we explore how the medicinal effects of the milkweeds interact with innate immunity and gut microbes of the butterflies, hypothesizing that the protective effect of the plant could in part be mediated by changes in immunity or the gut microbiome to a protective state. In terms of immunity, we find little evidence of a strong immune response towards the parasite, suggesting that the plants are not altering the immune response to a protective state. We, however, find evidence of the plants altering the community of microbes in the gut to a protective state. Taken together, these results highlight how immunity is one component of a complex array of animal defenses.