Plant-mediated synthesis of nanoparticles has gained much attentions due to its eco-friendliness, non-toxic, ease of preparation and biocompatibility. Phytochemicals has been adjudged to be useful as bio-reductants, stabilizers, and capping agents in the formation of nanoparticles. The aim of this study is to compare the antibacterial activities of biosynthesized Cerium oxide (CeO2NPs) and Zinc oxide nanoparticles (ZnONPs) against fish pathogens (Vibrio cholera strain RC3 and Escherichia coli strain C214). Qualitative analysis of Carica papaya leaf extract was performed to examine the biomolecules present, then biosynthesis was carried out. CeO2NP and ZnONP formed were characterized through UV-visible spectrophotometry, scanning electron microscopy, energy dispersive X-ray analysis, X-ray diffraction analysis, and Fourier transformed infrared spectroscopy to confirm the formation of the nanoparticles. The result revealed monodispersed, spherical shaped CeO2NPs with average size of 46.34nm, while ZnONP revealed cylindrical shaped nanoparticles with average size of 43.77nm. Antibacterial sensitivity test showed that CeO2NP has a higher antibacterial potential than ZnONPs on Vibrio cholera (13.00±1.41b and 10.00±1.41c) and E. coli (8.00±1.41b and 0.00±0.00a). In view of this outcome, it is therefore suggested that CeO2NP could be used effectively against Vibrio cholera strain RC3 and E. coli strain C214 than ZnONP with highly significant impact.