© 2021Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most important therapeutic agents used for the treatment of a variety of inflammation. Tenoxicam (TNX), which is used to relieve inflammation, swelling, and pain associated with rheumatoid arthritis, is a member of NSAIDs. In this study, copper(II), zinc(II), platinum(II) and palladium(II) complexes of TNX were synthesized and characterized by analytical and instrumental techniques (Ultraviolet and visible absorption spectra (UV–Vis), Liquid chromatography–mass spectrometry (LC-MS), Inductively coupled plasma - optical emission spectrometry (ICP-OES), Differential thermal analysis-Thermogravimetric analysis (DTA-TG)). Fourier-transform infrared (FT-IR) spectra of the complexes were measured and the outcome were supported by density functional theory computations. The proposed structure of these metal complexes are [Cu(TNX)2], [Zn(TNX)2], [Pt(TNX)2] and [Pd(TNX)Cl2]. The anti-inflammatory activities of the synthesized complexes, compared with the drug, were demonstrated for the first time. All metal complexes of the TNX acted more efficiently on the reduction of pro-inflammatory tumor necrosis factor (TNF)-alpha production than that of TNX. The highest anti-inflammatory potential was detected with [Cu(TNX)2]. The receptor-ligand interactions between TNX complexes and TNF-α were revealed by molecular docking calculations.