In this research two Indomethacin derivatives were synthesized, Indomethacin ethyl ester was synthesized by The Direct Esterification method by reacting indomethacin with ethanol within different conditions of time, molar ratios and solvents in acidic medium using homogeneous acid catalysts such as sulfuric acid and methane sulfuric acid and heterogeneous acid catalysts such as amberlyst- 15. Then indomethacin acid hydrazide was synthesized by condensing the previous ester with hydrazine hydrate and the best conditions were studied of time, molar ratios, solvents and different temperatures without using any catalyst.