Nonsteroidal 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.