The threat of antibiotic resistance is escalating, diminishing the effectiveness of numerous antibiotics due to the rapid development of resistant bacteria. In response, the use of green-synthesized nanoparticle, alone or combined with antimicrobial agents, appears promising. This study explores the effectiveness of zinc oxide nanoparticles (ZnONPs) synthesized using
Loranthus cordifolius
leaf extracts and subsequently coated with anethole. The fabrication of these nanoparticles was confirmed via UV-Vis, FTIR and TEM analyses, ensuring the nanoparticles were produced as intended. Utilizing a nanoprecipitation process that excludes evaporation and drying, a high drug loading capacity of 16.59% was accomplished. The encapsulation efficiency for anethole was recorded at 88.23 ± 4.98%. Antibacterial efficacy was assessed by com paring the green-synthesized ZnONPs (average size: 14.47 nm), anethole-loaded ZnONPs (average size: 14,75 nm), and commercially sourced ZnONPs. The ZnONPs with anethole demonstrated superior inhibition against all tested bacterial strains, including Gram-negative species like
Pseudomonas aeruginosa
and
Escherichia coli
, and Gram-positive species like
Bacillus subtilis
and
Staphylococcus aureus
, outperforming the commercially available ZnONPs. Additionally, anethole-coated ZnONPs showed the greatest inhibition of Gyr-B activity (IC50 = 0.78 ± 0.2 M), better than both green-synthesized and commercially available ZnONPs. These findings emphasize the enhanced antimicrobial properties of ZnONPs, particularly when combined with green synthesis and anethole loading, highlighting their potential in various biomedical applications.