The usage of mesoporous bioactive glasses (MBGs) containing a minor amount of therapeutic metal ions is increasingly important, with the purpose of imparting antibacterial activity and the simulation of osteogenesis and angiogenesis. In order to provide MBGs with enhanced biological functions, the framework of ternary SiO2-CaO-P2O5 mesoporous glass with a moderate amount of copper ions (5 mol %; 5Cu-MBGs) is obtained through a modified sol-gel procedure combined with evaporation-induced self-assembly (EISA). Unlike previous studies that primarily varied dopant concentration or surfactant removal routes, we systematically tuned the textural properties and local atomic structure of 5Cu-MBGs by employing different sol-gel catalysts: acetic acid, NH4OH base, both, or none. Structural and textural analyses revealed that the catalyst choice strongly governs the surface area, pore size, and silanol (Si-OH) density. In vitro bioactivity assays demonstrated that these parameters critically influence ion release kinetics and hydroxyapatite layer formation, while hemolysis tests confirmed that samples with a higher surface area and silanol content exhibited excellent blood compatibility. Notably, the acid-assisted route produced 5Cu-MBGs with exceptional textural features and abundant Si-OH groups, which synergistically promoted superior dissolution behavior, enhanced bioactivity, and biocompatibility. This study, to the best of our knowledge, is the first to establish catalyst selection during the sol-gel process as a rational design strategy for tailoring the biological responses of Cu-MBGs, thereby providing a novel pathway to engineer advanced biomaterials for bone regeneration and infection control.