Background and Objective: Glucosamine is a natural amino sugar that can prevent demolition in osteoarthritis. Considering the advantages of effervescent form of drugs, including attractiveness of effervescence and easiness of consumption, it was decided to formulate this drug as effervescent granules. Subjects and Methods: Flow, compactibility and solubility of the glucosamine powder were primarily tested. The experimental design was utilized to evaluate the effect of formulation factors on glucosamine granules. Using the cupermental drawing, 27 effervescent formulations were produced by dry granulation method. Independent variables were ratio of effervescent materials, ratio of dicalcium phosphate (DCP)/Mannitol and particle size and the responds were flow rate, pH and shelf-life. Using the common points of optimum responses, the best formulation was chosen and after physicochemical considerations, sweetener, colorant and flavoring agents were added.Results: Glucosamine powder had poor flow and compactibility characteristics while dissolved readily in water. Altering the ratio of effervescent materials had a little effect on flow rate, while the ratio of DCP/mannitol and particle size were more effective. All of the independent variables affected the shelf-life significantly while the ratio of DCP/mannitol was less effective.Conclusion: Factorial design was a proper method to achieve better results of glucosamine formulation in a short duration of time. In conclusion, considering the results of physico-chemical aspects, the formulation containing glucosamine, sodium bicarbonate, tartaric acid, citric acid, dicalcium phosphate, mannitol, PEG4000, aspartame, Tomate red as colorant and aromatic orange as flavorant, with the expiration date of 530 days was chosen as the best formulation.