Macromolecular of naturally occurring humic acid (HA) have garnered interest in the chemical, biological and medicine industry owing to their unique behavior, i.e., strong adsorptive and non-toxic nature. Here, we investigated the functionalization of organic (HA) with inorganic (ZnO) hybrid nanoparticles for topical and site-targeted delivery of ciprofloxacin by simple emulsification techniques. Ciprofloxacin (CIPRO)-encapsulated hybrid nanocarrier constitute an attractive novel drug delivery vehicle for sustained release of antibiotics to bacterial infection sites in an extended and controlled manner. The analytical characteristics of the designed system were thoroughly investigated by FTIR, XRD, SEM/EDAX, and TEM. The drug release of ciprofloxacin over 24 h was 87.5%, 98.03%, 97.44%, and 97.24% for pH 2.5, 5.5, 6.8, and 8.0, respectively. The antibacterial activities results confirmed that the CIPRO-encapsulated hybrid nanocarrier showed excellent growth inhibition against microorganisms. This hybrid nanocarrier loaded with antibiotics represents a promising approach for targeted and controlled drug delivery to infected sites.