This study reports the synthesis and characterization of two new organometallic Au (III) and Pt (II) complexes with 2‐acetylthiophene‐N(3)‐methylthiosemicarbazone (HL). The characterization of the compounds was performed by single‐crystal X‐ray diffraction and spectroscopic techniques (Fourier transform infrared (FT‐IR), UV–Vis, electrospray ionization (ESI)(+)‐mass spectrometry (MS), and nuclear magnetic resonance (NMR)). The MS data indicated the presence in the solution of the molecular ion [H2L]+ and characteristic fragmentations of the ligand. The thiosemicarbazone is coordinated to the Au (III) and Pt (II) in tridentate mode through the CNS chelating system. The two metal atoms show a distorted square geometry including chloride ion or triphenylphosphine to complete the coordination sphere. The 3D Hirshfeld surface and the 2D fingerprint results were analyzed quantitatively to verify interactions upon the molecular packing. The biological activity of the free thiosemicarbazone and their complexes have been evaluated against the MCF‐7 human cancer cell line. Molecular docking was used to predict the inhibitory activity of the compounds.