Bruxism-induced wear and microbial colonization of oral splints remain significant challenges in restorative dentistry. In this study, we developed a series of antibacterial nanocomposites based on a poly(ethylene terephthalate-co-1,4-cyclohexanedimethylene terephthalate) (PET-G) matrix incorporated with zinc oxide (ZnO) particles (3, 7, and 10 wt%), designed for the next generation of oral appliances. The composites were fabricated via a solvent-casting method followed by thermal processing. Differential scanning calorimetry (DSC) revealed that the amorphous nature and glass transition temperature (Tg ≈ 80 °C) of the PET-G matrix remained stable, ensuring excellent processability. While a minor decrease in Shore D hardness and flexural strength (up to 15%) was observed due to filler-induced structural discontinuity, the mechanical integrity remained within clinically acceptable limits. Crucially, the PET-G/ZnO composites exhibited potent antimicrobial activity; the 7 and 10 wt% loadings achieved a 100% reduction in Streptococcus oralis viability and significant inhibition of Candida albicans. These findings demonstrate that ZnO integration provides a dual-functional advantage—maintaining the thermoplastic versatility of PET-G while introducing critical bioactive properties, positioning these materials as a superior alternative for effective long-term bruxism therapy.