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Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.