Development of novel Schiff’s base Indole derivatives as Anti-inflammatory agents is critically needed to obviate the necessity of the potent anti-inflammatory agents. The aim of the study is associated to develop and evaluate Schiff’s base Indole derivatives as Anti-inflammatory agents using Schiff’s base synthesis approaches. each synthesized compound was characterized spectroscopically. In-silico docking analysis was performed to evaluate the potent anti-inflammatory agents via exploring interaction profile of each compounds with TNF-α protein followed by in-vivo estimation of active components against carrageenan induced paw edema. The outcome of the study showed that among different compounds, the compound such as C1IN, C2IN, C3IN, C7IN, C8IN and C11IN were found most active against COX-2 as well as paw edema induced by carrageenan.