AbstractTitanium alloys are commonly used as biomaterials in musculoskeletal applications, but their long‐term efficacy can be limited by wear and corrosion, stress shielding, and bacterial colonization. As a promising alternative, bulk metallic glasses (BMGs) offer superior strength and corrosion resistance, but the influence of their chemical composition on their bioactivity remains largely unexplored. This study, therefore, aims to examine how the surface chemistry of palladium (Pd)‐, platinum (Pt)‐, and titanium (Ti)‐based BMGs can steer their response to biological systems. The chemical composition of BMGs governs their thermophysical and mechanical properties, with Pd‐based BMGs showing exceptional glass‐forming ability suitable for larger implants, and all BMGs exhibiting a significantly lower Young's modulus than Ti‐6Al‐4 V (Ti64), suggesting a potential to reduce stress shielding. Although BMGs feature copper depletion at the near surface, their surface chemistry remains more stable than that of Ti64 and supports blood biocompatibility. Fibrin network formation is heavily dependent on BMGs’ chemical composition and Ti‐based BMGs support thicker fibrin network formation than Ti64. Furthermore, BMGs outperform Ti64 in promoting mineralization of human bone progenitor cells and demonstrate antimicrobial properties against Staphylococcus aureus in a surface chemistry‐dependent manner, thereby indicating their great potential as biomaterials for musculoskeletal applications.