New Guinea is the most biologically and linguistically diverse tropical island on Earth, yet the potential impacts of climate change on its biocultural heritage remain unknown. Analyzing 2353 endemic plant species distributions, we find that 63% of species are expected to have smaller geographic ranges by 2070. As a result, ecoregions may have an average of −70 ± 40 fewer species by 2070. Species with future geographic range contractions include 720 endemic plant species that are used by indigenous people, and we find that these will decrease in 80% of New Guinea’s 1030 language areas, with losses of up to 94 species per language area. To mitigate the threats of climate change on the flora, we identify priority sites for protected area expansion that can jointly maximize biodiversity and useful plant conservation.