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This study recommends Carbopol/zinc oxide (ZnO) hybrid nanoparticles gel as an efficient antibacterial agent against different bacterial species. To this end, ZnO nanoparticles were synthesized using chemical precipitation derived from a zinc acetate solution with ammonium hydroxide as its precipitating agent under the effect of ultrasonic radiation. The synthesized ZnO nanoparticles were stabilized simultaneously in a freshly prepared Carbopol gel at a pH of 7. The chemical composition, phase identification, particle size and shape, surface charge, pore size distribution, and the BET surface area of the ZnO nanoparticles, as well as the Carbopol/ZnO hybrid Nanoparticles gel, were by XRD, SEM, TEM, AFM, DLS, Zeta potential and BET instruments. The results revealed that the synthesized ZnO nanoparticles were well-dispersed in the Carbopol gel network, and have a wurtzite-crystalline phase of spherical shape. Moreover, the Carbopol/ZnO hybrid nanoparticles gel exhibited a particle size distribution between ~9 and ~93 nm, and a surface area of 54.26 m²/g. The synthesized Carbopol/ZnO hybrid nanoparticles gel underwent an antibacterial sensitivity test against gram-negative K. pneumonia (ATCC 13883), Bacillus subtilis (ATCC 6633), and gram-positive Staphylococcus aureus (ATCC 6538) bacterial strains, and were compared with ampicillin as a reference antibiotic agent. The obtained results demonstrated that the synthesized Carbopol/ZnO hybrid nanoparticles gel exhibited a compatible bioactivity against the different strains of bacteria.