A supramolecular complex (SFBZ) of fenbendazole (FBZ) with licorice extract and sodium dioctyl sulfosuccinate is prepared by mechanochemical method, and its anthelminthic activity and metabolism in sheep are studied. Physicochemical studies of SFBZ confirmed its improved solubility and a decrease in the particle size. FBZ and its metabolites are found to display enhanced absorption into the bloodstream. Their maximum concentration in the blood increases by a factor of 2.3–2.5, and the time required to reach this level increases. The efficacy of SFBZ on the laboratory model of Trichinella spiralis infection is 96.27% at a dose of 1 mg/kg a.i. (active ingredient), whereas the efficacy of the FBZ substance administered at the same dose is 13.70%. A single oral dose of 2.0 mg/kg (a.i.) of SFBZ is highly effective against nematodes in naturally infected sheep, as fecal analyses showed; while the FBZ substance revealed 95.97% efficacy at a dose of 5.0 mg/kg. The higher activity of SFBZ is related to its increased solubility and improved absorption in the animal body.