The antibacterial mechanisms of silver-doped bioactive glass-ceramic (Ag-BG) microparticles are explored in this work aiming to understand the mechanisms of inhibition against Methicillin-Resistant Staphylococcus aureus (MRSA). This work shows that the antibacterial properties were not limited to the release of silver ions but the combined action of several antibacterial degradation by-products. In particular, it presents the action of nano-sized debris that damages bacteria’s membrane, the osmotic effects, and the reactive oxygen species that cause oxidative stress and are responsible for almost 40% of the inhibition. Prolonged exposure of MRSA to Ag-BG, shows that MRSA undergoes phenotypic changes and genomic mutations increasing the sensitivity of bacteria rather than conferring resistance. Moreover, it was observed that Ag-BG allows the restoration of antibiotics that MRSA resists through a synergistic action. This synergy occurs with antibiotics that target cell-wall activity and is effective against bacteria being both in biofilm and planktonic form. A comprehensive understanding of the mechanisms of antibacterial activity will offer new insights towards tailoring biomaterials for applications to prevent or overcome infections and combat antibiotic resistance.