Background: Cordyline fruticosa (L.) A. Chev. (Asparagaceae) is a plant which is traditionally used for the treatmentof cough, bloody cough, diarrhea, dysentery, high fever, difficulties in urine, bloody urine, small pox, madness, skineruptions, joint pains, rheumatic bone pains, sore throat, neck pain, bleeding hemorrhoids and inflammation in thedigestive tract. Therefore, the present work aims to investigate the antidiarrheal and cytotoxic activities ofmethanolic extract of Cordyline fruticosa leaves in mice and brine shrimp, respectively.Methods: The effects of the methanol extract of Cordyline fruticosa leaves (MCFL) on castor oil-induced diarrhea,magnesium sulphate induced diarrhea and charcoal meal test in mice were investigated. In addition, brine shrimplethality bioassay method was used to evaluate cytotoxic activity of MCFL.Results: In castor oil induced diarrheal test, MCFL at the dose of 200, 400 and 800 mg/kg body weight significantly(∗P< 0.05, versus control) and dose-dependently reduced the frequency of diarrhea. The frequency of magnesiumsulphate-induced diarrhea was significantly reduced by MCFL at the dose of with 800 mg/kg. In the charcoal mealtest, the extract at the dose of 400 and 800 mg/kg body weight significantly (∗P< 0.05) reduced the distancetravelled by charcoal along the intestinal tract when compare with control. However, in brine shrimp lethality testafter 24 h, surviving brine shrimp nauplii were counted and LC50 was assessed. The extract exhibited considerabletoxicity towards brine shrimp with LC50 value of 355.7 μg/mL,with respect to standard vincristine sulfate (havingLC50 of 3.8 μg/mL).Conclusion: The results of present investigation suggest that methanolic extract of Cordyline fruticosa leavespossesses antidiarrheal and cytotoxic activities, confirming the traditional use of the plant in the treatment ofdiarrhea.