In this study, a novel drug delivery system based on zinc oxide nanoparticles (ZnO NPs) was developed for the enhanced delivery of cisplatin (CPT) to improve cancer treatment. The ZnO NPs were synthesized from guava leaf extract and then surface-functionalized with gallic acid (GA) to improve their biocompatibility and drug loading capacity. Pluronic F127, a biocompatible polymer, was then conjugated to the GA-modified ZnO NPs to further enhance their stability and cellular uptake. The resulting NPs were characterized by various techniques, including FT-IR, UV-Vis, SEM, TEM, H NMR, and DLS. The drug loading and release profiles of CPT from the NPs were investigated, showing high CPT loading capacity and pH-dependent release behavior. The cytotoxicity of the NPs was evaluated against various cancer cell lines, demonstrating enhanced cytotoxicity compared to free CPT. Overall, this study highlights the potential of GA and Pluronic-modified ZnO NPs as a promising drug delivery system for enhanced CPT delivery and improved cancer therapy.