Background: Newer antidiarrheal agents include the mucoprotectants gelatin tannate and xyloglucan. Methods: Rat models of cholera toxin (CT)-induced water secretion were used to evaluate the mucoprotective effects of gelatin tannate, xyloglucan, and related compounds. Results: Oral pretreatment for 4 days with gelatin tannate (250 and 500 mg/kg/day), but not tannic acid or gelatin (both 125 mg/kg/day), blocked CT-induced intestinal water secretion. CT-induced intestinal water secretion was also attenuated by oral xyloglucan 12.5 mg/kg + gelatin 125 mg/kg (6 h pre-CT) and gelatin 250 mg/kg (12 h pre-CT), and by local (intra-jejunal loop) administration of gelatin, gelatin tannate and xyloglucan concomitantly with CT. Conclusions: Gelatin tannate and xyloglucan + gelatin attenuated CT-induced intra-loop water secretion in this experimental model, supporting previous evidence that their mechanisms of mucosal protection are closely related to their chemical structures, which confer film-forming properties via the formation of mucoadhesive films.