Soil-transmitted helminth infections are neglected tropical diseases, afflicting over 1.5 billion people in developing countries. Children often endure the heaviest parasite burdens, suffering from malnutrition, stunted growth and cognitive impairment. The widespread use of anthelmintic drugs as preventative chemotherapy has accentuated low cure rates, high reinfection rates and increasing prevalence of anthelmintic-resistant species, particularly in Trichuris infection, highlighting an urgent need for novel treatments. Intestinal helminth infections are associated with changes in enteroendocrine cell (EEC) development and peptide hormone secretion. Furthermore, intraepithelial lymphocytes, found at the parasite intestinal barrier niche, have been shown to express receptors for the EEC derived incretin peptide hormone, glucagon-like peptide-1 (GLP-1). Recently GLP-1 receptor agonist (GLP-1rA) treatment has been shown to induce expulsion of a chronic low-dose Trichuris muris infection via the adaptive immune system and accelerated intestinal epithelial turnover. However, the effects of intestinal helminths on endogenous GLP-1 secretion are currently unknown. Furthermore, the efficacy of GLP-1rA treatment in individuals with high infection intensity, and against challenge infection, is yet to be investigated. A small intestinal organoid platform was used to investigate the effects of intestinal helminth antigen on GLP-1 secretion. The mouse model of human trichuriasis, Trichuris muris, was employed to investigate the potential for the GLP-1rA, lixisenatide to induce protective effects against challenge infection, and, via rIL-12-pretreatment, to investigate the efficacy of lixisenatide against a chronic high-dose infection. Trichinella spiralis was shown to increase GLP-1 secretion from EECs in the small intestine through a mechanism mediated by bitter taste receptors. In vivo experimentation demonstrated that lixisenatide treatment drives a reduction in worm burden in a chronic, high-dose T. muris infection, and induces CD4+ T cell-mediated protection against challenge infection. These data provide further evidence that this treatment may provide an exciting novel option for the treatment of intestinal STH infection, with efficacy in reducing high intensity infection and providing some protection against reinfection, crucial effects that current anthelmintic treatments lack. GLP-1rAs are already approved for the treatment of type 2 diabetes mellitus and obesity, which would allow for rapid and straightforward repurposing of this drug class for the treatment of Trichuriasis afflicting livestock and humans worldwide.