<p dir="ltr">Bulk metallic glasses (BMGs) possess higher strength than crystalline alloys because crack propagation is halted through a grain boundary-, crystal defect-free amorphous structure. Nanocrystal inclusions can further enhance mechanical properties. Here we investigate how the formation of nanocrystals into a Ti41.2Zr10.6Cu39.1Pd9.1 BMG matrix via controlled annealing that leads to devitrification of the bulk microstructure, as well as chemical changes to the surface oxide layer, affects mechanical and biological performance. The BMG nanocrystalline composite (BMGC, 12.8% crystallinity produced via annealing at 415 °C for 5 min, based on crystallisation kinetics studies) was compared to the fully amorphous BMG and the fully crystalline counterpart (annealed at 415 °C and 60 min). BMGC fracture strength (1,374.6 MPa) was higher than that of the amorphous BMG (1,303.1 MPa) and the fully crystalline specimen (644.4 MPa). Young’s moduli correlated negatively with the degree of crystallisation (78.3-66.2 GPa). The results from in vitro tests on MC3T3-E1 illustrate that the surface chemistry plays a crucial role enhancing osteoblastogenesis: the presence of Zr oxides, wettable surfaces and large values of polar component of Surface Free Energy due to the nanocrystals, and a thinner oxide layer with low concentrations of CuxO, positioned BMGC as the preferred substrate. Tailoring amorphicity-to-crystallinity ratio in a Ti-Zr-Cu-Pd BMG is a route to create multifunctional substrates.</p>