Background and Objectives: In recent years, the attention of the scientific community has been attracted by cerium(IV) oxide nanoparticles (CeO₂ NPs), which demonstrate great potential for use in biomedicine due to their unique biological properties such as antioxidant and antibacterial activity. The development of biomaterials that combine the properties of polymers and the unique characteristics of CeO₂ NPs opens up new horizons for applications in biomedicine. A thin layer of polymers preserves the catalytic activity of cerium oxide without blocking the path of electronic charge transfer on the surface of nanoparticles. The relevance of the development of CeO₂ NPs with a polymer shell lies in the fact that polymers can bind to various medicinal and bioactive substances, becoming drug carriers. This work describes the preparation of CeO₂ NPs with various polymers in order to study how the composition and structure of the polymer affect the size and charge of the resulting nanoparticles. The variability of the properties of CeO₂ NPs will make it possible to test them for the encapsulation of other substances, including drugs, in order to identify optimal polymers. Materials and Methods: Cerium(III) nitrate hexahydrate Ce(NO₃)₃ · 6H₂O was used as a precursor for the synthesis of CeO₂ NPs. Four different polymers were used for the syntheses: polyacrylic acid (PAA), polyethylene glycol (PEG), poly(isobutylene-alt-maleic anhydride) (PIMA). The synthesis was carried out in ammonium hydroxide (28–30%). CeO₂ NPs with a polymer shell were obtained by chemical deposition. Polymer solutions were prepared and mixed with a 1 M solution of Ce(NO₃)₃. With continuous stirring, the mixture was added to the ammonium hydroxide solution, after which ethanol was added and left under stirring for 24 hours at room temperature. Results: We have presented the synthesis of cerium oxide nanoparticles in the presence of polymers of various compositions and molecular weights to study their effect on the structure and size of nanoparticles. During the synthesis, it has been revealed that the optimal concentration of cerium(III) nitrate for syntheses is 1 M. The influence of the environment on the possible agglomeration of nanoparticles during purification and further storage has been studied. The best media for storing and purifying nanoparticles are water and phosphate-buffered saline. The size and morphology of the resulting polymer-coated CeO₂ NPs have been studied by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS). TEM images show nanocrystals measuring about 10 nm in all four samples. SEM images show the presence of particles with a size of about 20–30 nm in all four samples. DLS analysis has shown that the smallest particles were formed with polyacrylic acid and poly(isobutylene-alt-maleic anhydride). Conclusions: The results of the study have demonstrated that for the synthesis of CeO₂ NPs with a polymer coating it is better to use PAA and PIMA polymers since smaller particles are formed. It has been found that it is optimal to use 1 M Ce(NO₃)₃ for syntheses, and the best media for purification and storage of CeO₂ NPs are water and FSB.