A series of 5‐hydroxy‐4‐(N‐substituted carbothioamide) pyrazole derivatives (HL¹–HL⁵) and their iron(III), nickel(II), and copper(II) complexes have been synthesized. Structural elucidations of the isolated ligands and their complexes are basically accomplished by FT‐IR, ¹H NMR, ¹³C NMR, UV–Vis, ESR, MS, and thermogravimetric analysis (TGA). The analytical data propose the stoichiometries 1:3 (M:L) for Fe(III) and 2:3 for both Ni(II) and Cu(II) complexes. The spectral data substantiate the bidentate coordination mode for all ligands towards metal ions via S and O atoms of CS of the carbothioamide group at pyrazole‐C₄ and OH group at C(5) where deprotonation occurs from the enolic tautomer on chelation. Likewise, bidentate pattern of a bridged acetate group is confirmed in the case of Ni(II) and Cu(II) complexes. The magnetic moment values validate high spin octahedral geometry for Fe(III) complexes whereas the diamagnetic feature of Ni(II) complexes is in conformity with the square planar symmetry of low spin state. ESR spectra of all Cu(II) complexes support their existence in distorted square planar geometry with a considerable electron exchange between two copper ion centers of dinuclear type. TGA and DTG analysis of six complexes display their considerable thermal stability. Besides, the in vitro biological screening effects of some selected compounds are tested against various human pathogen microorganisms. Among the ligands, HL⁵ exhibits the greatest antibacterial activity against two Gram‐positive species (Bacillus subtilis and Staphylococcus aureus) and one Gram‐negative (Proteus vulgaris) in comparison with gentamicin drug. Furthermore, IC₅₀ values of [Cu₂(L⁵)₃(OAc)] complex reveal its significant anticancer activity against the three tumor cell lines HCT‐116, MCF‐7, and HepG‐2 compared with imatinib and cisplatin as positive controls. Finally, the optimized structures of all ligands and their molecular electrostatic potential surfaces are established by utilizing density functional theory (DFT).