Diarrhea is a global epidemic. Majority of the populace in developing Countries including Nigeria depend on Napoleona imperialis as a safer, more effective and affordable alternatives for treatment of diarrhea. This study evaluated the antidiarrheal potential of ethanol (leaf) extract and fractions of N. imperialis in Swiss albino mice. Acute toxicity test was performed to determine safe dose range before in vivo experiments. Castor-oil induced diarrhea and charcoal meal gastrointestinal motility test models were used. Antimicrobial activity on bacteriaimplicated diarrhea, and HPLC analysis of the aqueous fraction (AF) were also evaluated. The result of the acute toxicity tests show that no death occurred at the test doses. Preliminary antimicrobial screening shows that the inhibitory zone diameter (IZD) of the extract has a weak antibacterial activity against sample organisms. The presence of procyanidin, 9-alpha-OH-pinoresinol, isoprunetin and ellagic acid derivatives in the aqueous fraction were highlighted by the HPLC analysis. The AF produced more significant (P<0.05) decrease in diarrhea than the other groups. This study shows that N. imperialis possesses antidiarrheal activity and hence justifies its folkloric use in the treatment of diarrhea.