Gadolinium (Gd) nanoparticles (NPs) are increasingly considered as a viable alternative to clinically employed Gd chelates in magnetic resonance imaging (MRI). The utilisation of these materials as contrast agents offers several advantages including lower toxicity, prolonged circulation time, and a sufficiently high Gd content, thereby enhancing disease imaging during MRI diagnosis. Therefore, this study synthesised Gd NPs using the hydrothermal method based on the response surface methodology Box-Behnken design (RSM-BBD) to determine the optimal conditions. In this experimental design, three independent variables, the mass of Gd2O3 (g), the synthesis temperature (°C) and time (h), were optimised to obtain sufficiently sized nanoparticles for further biomedical applications. In addition, polyethene glycol-6000 (PEG-6000) was used as a stabiliser to form uniformly sized nanoparticles. The optimal conditions were 0.4910 g of Gd2O3, a temperature of 180 °C, and a synthesis time of 7 h. Characterisation by scanning electron microscope-energy dispersive X-ray (SEM-EDX) and transmission electron microscope (TEM) demonstrated that the Gd NPs were spherical with a size range below 20 nm. Fourier transform infrared (FTIR) spectroscopy identified PEG molecules with low intensity on the Gd NPs and the obtained zeta potential value was +36.7±0.802 mV. The RSM-BBD analysis applied in this study facilitated the determination of the optimal synthesis conditions.@en