Background: Emesis is a complex and distressing protective mechanism that helps to remove toxic substances from the stomach and prevent further ingestion. The emetics and cathartics are predominantly used for accidental and intentional ingestion of poisons or toxins. The availability and usage of emetics in humans are limited because of their side effects. Therefore, to treat poisoned people, we need effective medications. Sapindus emarginatus Vahl., often called soapnut, is a member of the Sapindaceae family. They have historically been used as emetic, antipruritic, laxative, antifertility, and anti-inflammatory medicines. Objective: This study aims to assess the gut serotonin level and emetic effect of Sapindus emarginatus hydroethanolic pericarp extract (HESE) by using animal models. Methods: Gravimetric analysis was used to determine the HESE's saponin content. The emetic effect of the HESE at a dose of 250, 500, 1000, and 2000 mg/kg was evaluated by copper sulfateinduced emesis in the chick model and cisplatin-induced emesis in the rat-pica model. The serotonin level in rat intestinal mucosa was measured by spectrofluorimetry. Results: HESE was estimated to contain 11.92% saponin. The extract at high doses of 1000 and 2000 mg/kg showed emetic activity evidenced by increased frequency of retching in chick, increased kaolin intake, and anorexia in the rat-pica model. The extract showed a significant increase in serotonin levels in the proximal part of the small intestine in comparison with normal animals. Conclusion: According to the results of the current investigation, which employed various animal models, the HESE demonstrated appreciable emetic activity. The extract at a high dose showed a significant emetic effect due to increased serotonin levels in the gut. The HESE was discovered to be a strong contender for the treatment of poisoned patients. More research are required to validate their adverse effects of frequent usage.