The aim of the study was to synthesize cobalt and manganese complexes of indomethacin and their biological activity screening to uncover. The structures of metal complexes were elucidated by FT-IR, UV-Vis and atomic absorption spectroscopy, X-ray diffraction and calorimetric DSC. Heat radiant tail-flick test for local analgesic activity of cobalt complex of indomethacin in the doses of 50 and 100 μg/mL demonstrated potent local analgesic response. Manganese complex of indomethacin exhibited similar potent of activity at the dose of 100 μg/mL. Anti-inflammatory study of the indomethacin-manganese and indomethacin-cobalt complexes demonstrated their activity (paw edema inhibition of 71.67% at 20 mg/kg dose in the 1 h and 83.33% at 10 mg/kg dose in the 4 h) comparable with the standard diclofenac sodium. Gastrointestinal efficacy of cobalt and manganese complexes was close to that of indomethacin.