In the last decade, the publications presenting novel physical and chemical aspects of gadolinium-based oxide (Gd2O3) and oxysulfide (Gd2O2S) particles in the micro- or nano-scale have increased, mainly stimulated by the exciting applications of these materials in the biomedical field. Their optical properties, related to down and upconversion phenomena and the ability to functionalize their surface, make them attractive for developing new probes for selective targeting and emergent bioimaging techniques, either for biomolecule labeling or theranostics. Moreover, recent reports have shown interesting optical behavior of these systems influenced by the synthesis methods, dopant amount and type, particle shape and size, and surface functionality. Hence, this review presents a compilation of the latest works focused on evaluating the optical properties of Gd2O3 and Gd2O2S particles as a function of their physicochemical and morphological properties; and also on their novel applications as MRI contrast agents and drug delivery nanovehicles, discussed along with their administration routes, biodistribution, cytotoxicity, and clearance mechanisms. Perspectives for this field are also identified and discussed.