Objective:To investigate the pharmacological basis of its uses of Phyla nodiflora (P. nodiflora) for the treatment of anomalies predominantly by smooth muscle containing tissues such as gastrointestinal/vascular/broncho spasm and cardiovascular modulation. Methods:The crude hydroalcoholic extract of P. nodiflora (Pn.Cr) and its fractions were evaluated on isolated rabbit jejunum,rat trachea,aorta and atrium. To access the con-tractile or relaxant effects of testing materials,the tissues were mounted in isolated organ bath and responses were recorded with transducers coupled with data acquisition system. BALB/c mice were challenged with castor oil for the assessment of in-vivo antidiarrheal activity. Normotensive rats were used for in-vivo hypotensive study. Results:Hydroalcoholic extract of Pn.Cr at variable concentrations inhibited the natural spontaneous rhythm and 80 mmol/L K+ mediated contractions in isolated segment of jejunum with EC50 values of 3.18 and 1.91 mg/mL respectively. Verapamil,a Ca2+channel blocker,demonstrated akin patt in jejunum and therefore possibly suggesting calcium blocking activity. On isolated rat tracheal tissue,Pn.Cr showed relaxation of high-K+ and carbachol mediated contractions (EC50 values:1.24 and 2.42 mg/mL). Pn.Cr treatment relaxed the rat aortic ring in a cumulative doses with high-K+ and phenylephrine-induced contractions (EC50 values 0.25 and 0.92 mg/mL). Activity based fractionation of Pn.Cr showed that dichloromethane fraction was more potent for relaxing the tissues spasm compared to aqueous fraction. In-vivo experiments,significant pro-tection by Pn.Cr (P < 0.05) was observed in castor oil-induced diarrhea (50–500 mg/kg) whereas hypotensive effect in anesthetized rats was seen at the dose range of 1–10 mg/kg of Pn.Cr (P < 0.05). Conclusion:This study suggests the blockage of calcium channel in the smooth muscles as a pharmacological application to make usage of P. nodiflora in the management of diarrhea,asthma and hypotensive effect.