Yamoa™ (ground bark of Funtumia elastica tree) is marketed and sold as a dietary supplement with anecdotal therapeutic effects in the treatment of asthma and hay fever. We determined that Yamoa™ and Yamoa™-derived polysaccharides affected innate immunity, in part, by priming γδ T cells. Gene expression patterns in purified bovine γδ T cells and monocytes induced by Yamoa™ were similar to those induced by ultrapure lipopolysaccharide (uLPS). In the presence of accessory cells, Yamoa™ had priming effects that were similar to those of LPS on bovine and murine γδ T cells, but much more potent than LPS on human γδ T cells. The bioactive component of Yamoa™ was delineated to a complex polysaccharide fraction (Yam-I). Intraperitoneal injection of Yamoa™ and Yam-I in mice induced rapid increases in peritoneal neutrophils directed by changes in chemokine expression. In support of a unique agonist found in Yam-I, similar peritonitis responses were also observed in TLR4- and MyD88-deficient mice. Therapeutic treatment with Yam-I resulted in decreased bacterial counts in feces from mice with Salmonella enterica serotype typhimurium (ST)-induced enterocolitis. This characterization of the immune stimulatory properties of polysaccharides derived from Yamoa™ suggests mechanisms for the anecdotal positive effects of its ingestion and that these polysaccharides show potential for application in innate protection from disease.