Every year about 2 billion cases of diarrhoea are diagnosed worldwide. Despite being an easily preventable and treatable disease, diarrhoea is the second leading cause of mortality, after pneumonia, in children below the age of 5 years. Annually, diarrhoea kills 1.5 million children; a toll greater than that of AIDS, malaria, and measles combined. In recognition of this danger, the UN’s Millennium Development Goal (MDG) number 4 aims to reduce childhood mortality by 2/3 by the year 2015. Recent estimates show minimal progress, and the MDG is likely to be missed. It is therefore necessary to review existing strategies and formulate newer ones. Recent years have seen a surge in interest in folk medicine (ethnopharmacology), especially the identification and evaluation of commonly available natural drugs, as alternative anti-diarrhoeal therapies. Mango fruit (Mangifera indica) seed has been used as an anti-diarrhoea remedy. The mechanism of action is, however, uncertain. The present study sought to investigate the in vitro effect of Mangifera indica seed extract on intestinal motility, and to elucidate its mechanism of action, and potential adverse effects on the heart.