Coumarin is highly distributed in nature, notably in higher plants. The biological features of coumarin include antibacterial, anticancer and antioxidant effects. It is well known that metal ions present in complexes accelerate the drug action and the efficacy of organic therapeutic agents. The main aim of the current study is the synthesis of different complexes of the interaction between ciprofloxacin hydrochloride (CIP) and coumarin derivative 7-hydroxy-4-methylcoumarin (HMC) with Zr(IV). The chelates of CIP with Zr(IV) were prepared and characterized by elemental analysis, melting point, conductance measurements, spectroscopic techniques involving IR, UV-Vis, 1H NMR, and thermal behavior (TG-DTG) in the presence of HMC, dimethylformamide (DMF), pyridine (Py), and triethylamine (Et3N). Results of molar conductivity tests showed that the new synthesized complexes are electrolytes with a 1:1 or 1:2 electrolyte ratio, with the chloride ions functioning as counter ions. According to IR spectra, CIP acts as a neutral bidentate ligand with Zr(IV) through one carboxylato oxygen and the carbonyl group, HMC as a monodentate through the carbonyl group, and DMF through the oxygen atom of the carbonyl group and the N atom of Py and Et3N. The thermal behavior of the complexes was carefully investigated using TG and DTG techniques. TG findings signal that water molecules are found as hydrated and coordinated. The thermal decomposition mechanisms proposed for CIP, HMC, and Zr(IV) complexes are discussed and the activation energies (Ea), Gibbs free energies (ΔG*), entropies (ΔS*), and enthalpies (ΔH*) of thermal decomposition reactions have been calculated using Coats–Redfern (CR) and Horowitz– Metzeger (HM) methods. The studied complexes were tested against some human pathogens and phytopathogens, including three Gram-positive bacteria (Bacillus subtilis, B. cereus, Brevibacterium otitidis) and three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae), and compared to the free CIP and HMC parent compounds.