Inflammation is a crucial physiological process that, when dysregulated can lead to chronic diseases such as arthritis, asthma and inflammatory bowel disease. This study focused on the design, synthesis and evaluation of novel xanthone-thiazole hybrid derivatives as potential anti-inflammatory agents using a straightforward experimental procedure. Anti-inflammatory activity was assessed through in silico, in vitro and in vivo methods. Out of 50 designed compounds, six showed significant in silico results and were synthesized for further evaluation. Docking experiments, using PDB ID: 2VCX and compared to diclofenac, identified compound G9 with the highest docking score of -10.9 kcal/mol, followed by G1 (-9.9 kcal/mol), G2 (-10.4 kcal/mol), G4 (-10.0 kcal/mol), G5 (-9.9 kcal/mol) and G7 (-10.3 kcal/mol). In vivo studies demonstrated that G9, especially at 110 mg/kg, exhibited sustained anti-inflammatory effectiveness (30.97 % at 2 h, decreasing to 1.36 % at 24 h), comparable to diclofenac. These findings highlight the potential of xanthone-thiazole hybrids as new anti-inflammatory drugs. The integration of in silico methods with experimental synthesis and testing proved effective, paving the way for further research to optimize synthesis, improve pharmacokinetic profiles and conduct clinical trials to ensure safety and efficacy.