There are nearly 7,400 languages in the world and over 30% of these will no longer be spoken by the end of the century1. So far, however, our understanding of whether language extinction may result in the loss of linguistically-unique knowledge remains limited. Here, we ask to what degree indigenous knowledge of medicinal plants is associated to individual languages and quantify how much indigenous knowledge may vanish as languages and plants go extinct. Focussing on three independent re-gions that have a high biocultural diversity —North America, northwest Amazonia, and New Guinea—we show that >75% of all 12,495 medicinal plant services are linguistically-unique, i.e., only known to one language. Whereas most plant species associated with linguistically-unique knowledge are not threatened, most languages that report linguistically-unique knowledge are. Our finding of high uniqueness in indigenous knowledge and strong coupling with threatened languages suggests that language loss will be even more critical to the extinction of medicinal knowledge than biodiversity loss.