This chapter explores strategies to control the defect structure and redox properties of CeO2-x nanocrystals, focusing on their role in modulating interaction with reactive oxygen species (ROS). Ultraviolet (UV) irradiation was shown to induce Ce4+ → Ce3+ transitions and increase the content of Ce3+-Vo-Ce3+ complexes enhancing the antioxidant activity of nanocrystals against hydroxyl radicals and superoxide anions. The redox behavior of CeO2-x was further demonstrated to be strongly pH-dependent: at neutral and alkaline conditions, catalase- and superoxide dismutase (SOD)-like activities dominate, while in acidic media, prooxidant effects emerge due to hydroxyl radical formation. This dual activity highlights the potential of nanoceria as a selective therapeutic agent, capable of protecting normal cells while promoting oxidative stress in cancer cells. Finally, the chapter discusses the application of CeO2-x and Eu3+-doped CeO2-x nanocrystals as reversible luminescent sensors for hydrogen peroxide, emphasizing the influence of particle size, temperature, and UV irradiation on sensitivity and recovery rates. Together, these findings provide fundamental insights into the tunable redox chemistry of cerium oxide nanocrystals with implications for biomedical, catalytic, and sensing applications.