Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. Cisplatin-loaded nanoparticle formulations were optimized utilizing response surface methods and the central composite rotating design model. This study employed a central composite rotatable design with a three-factored factorial design with three tiers. Three independent variables namely drug polymer ratio, aqueous organic phase ration, and stabilizer concentration were used to examine the particle size, entrapment efficiency, and drug loading of cisplatin PLGA nanoparticles as responses. The results revealed that this response surface approach might be able to be used to find the best formulation for the cisplatin PLGA nanoparticles. A polymer ratio of 1:8.27, organic phase ratio of 1:6, and stabilizer concentration of 0.15 were found to be optimum for cisplatin PLGA nanoparticles. Nanoparticles made under the optimal conditions found yielded a 112 nm particle size and a 95.4 percent entrapment efficiency, as well as a drug loading of 9 percent. The cisplatin PLGA nanoparticles tailored for scanning electon microscopy displayed a spherical form. A series of in vitro tests showed that the nanoparticle delivered cisplatin progressively over time. According to this work, the Response Surface Methodology (RSM) employing the central composite rotatable design may be successfully used to simulate cisplatin-PLGA nanoparticles.