Inflammation can be defined as a complex biological response that is produced by body tissues to harmful agents like pathogens, irritants, and damaged cells and thereby acts as a protective response incorporating immune cells, blood vessels, and molecular mediators. Histamine, serotonin, bradykinin, leukotrienes (LTB4), prostaglandins (PGE2), prostacyclins, reactive oxygen species, proinflammatory cytokines like IL-1, IL-11, TNF- anti-inflammatory cytokines like IL-4, IL-10, IL-11, IL-6 and IL-13, etc. all have different effects on both pro and anti-inflammatory mediators. Incorporation of combinatorial chemistry and computational studies have helped the researchers to design xanthones moieties with high selectivity that can serve as a lead compound and help develop potential compounds that can act as effective COX-2 inhibitors. The study aims to design and develop different series of substituted hydroxyxanthone derivatives with anti-inflammatory potential. The partially purified synthetic xanthone derivatives were orally administered to the carrageenan induced paw oedemic rat models at the dose of 100 mg/kg, and their effect in controlling the degree of inflammation was measured at the time interval of 30 min, 1, 2, 3, 4 and 6 hrs. respectively. Further, these compounds were also subjected to modern analytical studies like UV, IR, NMR and mass spectrometry or their characterization. The results drawn out of the in silico, in vitro, in vivo and analytical studies concluded that the hydroxyxanthone derivatives can obstruct the enzyme COX-2 and produce anti-inflammatory action potentially. With the aim to evaluate the compounds for their anti-inflammatory activity, it was observed that the newly designed xanthonic compounds also possess a safe toxicity margin and hence can be utilized by the researchers to develop hybrid xanthonic moieties that can specifically target the enzyme COX-2.