This study aims to evaluate the antihistaminic potential of the plant extract from Lannea coromandelica using both in vitro and in vivo models. In vitro antihistaminic effects were studied using isolated guinea pig ileum to assess dose-dependent inhibitory impacts on histamine-induced contractions. Mast cell density was evaluated using a mast cell count model, calculating the average number of mast cells per unit area in the mesentery. For in vivo assessments, a histamine aerosol-induced bronchospasm model in guinea pigs was used, where pre-convulsive dyspnea (PCD) onset time was noted as pre-convulsive time (PCT). Additionally, a clonidine-induced mast cell degranulation model in rats was employed, with cells stained using 1% toluidine blue to count intact and degranulated mast cells. The Lannea coromandelica extract exhibited a dose-dependent inhibition of histamine-induced contractions in isolated guinea pig ileum. Similarly, the extract inhibited mast cell degranulation in a dose-dependent manner, with a higher dose of 400 mg/kg proving more effective than a lower dose of 200 mg/kg. Acute toxicity studies confirmed the safety of the extract at moderate doses, revealing no toxic symptoms at a dosage of 2000 mg/kg body weight. Importantly, the extract significantly increased PCT in guinea pigs and reduced the percentage of disrupted mast cells induced by clonidine. Lannea coromandelica shows promising antihistaminic properties, effectively inhibiting histamine-induced bronchospasm and mast cell degranulation, which can be an option for the development of antiasthmatic drugs.