Poly-(D, L-lactic-co-glycolic) acid (PLGA)-loaded nedaplatin nanoparticles (PLGA-NDP) were prepared. The details of the preparation and characterisation of PLGA-loaded Nedaplatin nanoparticles formed and optimised by the double emulsion technique and Box–Behnken design with poly-(D, L-lactic-co-glycolic) acid as a polymer and polyvinyl alcohol (PVA) as surfactant agents were investigated. The morphology and elemental distribution, physical state, internal structure, encapsulation efficiency, and release profile were examined through sequential tactics such as Scanning Electron Microscopy-Energy Dispersive X-ray, Dynamic light scattering, Thermogravimetric analysis- Differential thermal analysis, Fourier-Transform Infrared Spectroscopy, UV-VIS spectroscopy, and in-vitro drug release study, respectively. Four factors at four levels were used in the Box-Behnken design to calculate the central point. The interaction between these factors significantly enhanced the results. The response of the optimised condition provided an accurate prediction, and the experiment was conducted further. The design was validated, and satisfactory agreement was observed between the predicted and experimental values. The obtained results provide evidence of a new geometric construction of PLGA-loaded nedaplatin nanoparticles with enhanced efficiency when compared to the reported research articles related to nedaplatin in cancer studies. Therefore, these findings and techniques are useful for the preparation of NPs.