Various substituted diphenyl bisamidines were prepared and tested for antiamoebic activity in Golden hamsters and Wistar rats. Compounds 10 showed in vitro activity at 100 μg/mL and displayed excellent in vivo activity against hepatic infection in the hamster. Its in vivo activity against intestinal amoebiasis in the experimental rat was superior to metronidazole and was comparable to diloxanide furoate. The less pronounced in vitro activity, and comparable in vivo activity of compound 10 with respect to the standard drugs, may be due to some of its metabolites.