Soil-transmitted helminths composed of three major groups - hookworms, whipworms and roundworms - form one of the most important infectious agents causing serious global health problems, particularly in developing and tropical regions of the world. The rodent parasites Nippostrongylus brasiliensis and Trichuris muris have been used as experimental models for human hookworm and whipworm, respectively, because of their similar life cycles and ease of maintenance in laboratory rodents. The adult worms live in the intestine of the host and release excretory/secretory products (ESP), which represent the major host-parasite interface. While studies on parasite-host interactions have traditionally focused on proteins, we focus on the characterization of small extracellular vesicles (EVs) that contain protein, lipids and nucleic acids. Here, we demonstrated the presence of helminth EVs as a component of the ESP. We generated comprehensive proteomic datasets for Trichuris and Nippostrongylus ESP and EVs, and RNA-seq data for Trichuris EVs. Recent research has shown that parasitic helminths communicate with their surrounding host cells via the secretion of EVs, possibly via release of EV genetic material inside the host target cell. Helminths have evolved strategies to manipulate the hosts’ immune system towards an immunoregulatory phenotype, which can have beneficial effects for both the parasite and the host. Consequently, there is interest in harnessing the immunoregulatory capabilities of helminths for the development of novel therapies for autoimmune, allergic and even metabolic diseases. Both porcine whipworms and human hookworms have proven effective in early stage clinical trials at treating a range of inflammatory diseases, and hookworm ESP has been shown to protect against various immunological disorders in animal models. We conducted a proof-of-principle experiment to evaluate if hookworm EVs confer protection in a murine model of colitis. Furthermore, a deep understanding of helminth EVs will reveal potential application in helminthic drug development and vaccine design.