Background: Orally disintegrating tablets (ODTs) are a modern form of tablets that when placed in the oral cavity, disperses rapidly. These tablets have advantages, particularly good applications for children and old patients who have a complication in chewing or swallowing solid dosage forms. The aim of this study was to design, formulate, and evaluate the physicochemical properties of 5 mg montelukast ODTs for the prevention of asthma and seasonal allergies. Methods: Formulations were prepared with different amounts of super disintegrating agents and effervescent bases as disintegrant agents. Flowability and compressibility of mixed powders were evaluated. The prepared formulations were tested for hardness, thickness, friability, weight variation, drug content, wetting time, disintegration time, dissolution study, and moisture uptake studies. Results: The compressibility index and angle of repose were in the range of 15.87%-23.43% and 32.93-34.65, respectively. Hardness, thickness, friability, wetting time, and content uniformity of formulations were in the range of 33.7-37.1 N, 3.00-3.81 mm, 0.27%-0.43%, 31-50 s and 96.28%-99.90%, respectively. Disintegration time of the tablets prepared with super disintegrating agents, effervescent bases, and combination of two were in the range of 30-50, more than 60 and 20-36 s, respectively. Conclusions: Mixture of powders and tablets passed all the specified tests. The results showed formulations prepared by super disintegrating agents and super disintegrating agents with effervescent bases had shorter disintegration time compared to formulations with effervescent bases alone.