This investigation probes the impact of trace addition (0.10 wt%) of the rare earth elements scandium (Sc) and yttrium (Y) on microstructure, mechanical properties, and biocompatibility of the newly designed beta-type (fi) Ti-24Nb-38Zr-2Mo alloy (TNZM) developed for orthopedic applications. Results indicated that both Sc and Y addition reduced average grain size, but their mechanisms were different. Sc showed solid solution strengthening, which caused increases in microhardness, tensile strength, tensile yield strength, ductility and compressive yield strength of TNZMS, without any change to Young's modulus (E). Conversely, Y precipitated as Y-rich oxides in grain boundary and internal region of TNZMY, which did not improve tensile strength and ductility but increased E. These were caused by heterogeneously distributed, large, Y-rich oxides; also, the fracture and separation of Y-rich oxides during deformation. Cytocompatibility assessments indicated all investigated Ti alloys possess good cytocompatibility, which exceeded control values. Given this, Sc is considered a potential alloying element for strengthening biomedical TNZM.