Since the last 41 years, Ibuprofen has been one of the most widely used Non-Steroidal Anti-Inflammatory Drug (NSAID) due to its anti-inflammatory actions. As all the NSAIDs are suffering from the deadlier GI toxicities, Ibuprofen also is no exception to these toxicities. The free –COOH group is thought to be responsible for the Gastrointestinal (GI) tract toxicity associated with all the traditional NSAIDs. Therefore, the main aim of this study was to develop new chemical entities as potential anti-inflammatory agents with less GI toxicities. In this article, synthesis of a series of Hybrid molecules containing important pharmacophore of Ibuprofen and substituted diaryl rings on 5-membered heterocycle similar to coxibs and Nitric oxidereleasing moiety are described. All the synthesized compounds were tested in vivo for their anti-inflammatory, analgesic, ulcerogenic properties, and histopathological studies and in vitro for their nitric oxide-releasing properties. Out of the six synthesized compounds, four compounds showed significant anti-inflammatory and analgesic activity which was compared with standard. All the synthesized compounds exhibited significant nitric oxide-releasing and reduced GI ulcerogenic activity.