<jats:p>(1) Dental caries, periodontitis, or peri-implantitis are commensal infections related to oral biofilm former bacteria. Likewise, magnesium oxide nanoparticles (MgO-NPs) were studied to introduce them to the antibacterial properties of a few microorganisms. Considering this, the purpose of the present investigation was to determine the antibacterial properties of MgO-NPs on representative oral strains. (2) Methods: MgO-NPs with a cubic crystal structure were obtained by magnesium hydroxide mechanical activation. After synthesis, the MgO-NPs product was annealed at 800 °C (2 h). The MgO-NPs obtained were tested against ten oral ATCC strains at ten serial concentrations (1:1 20.0–0.039 mg/mL per triplicate) using the micro-broth dilution method to determine the minimal inhibitory concentration (MIC) or minimal bactericidal concentration (MIB). Measures of OD595 were compared against each positive control with a Student’s t-test. Viability was corroborated by colony-forming units. (3) Results: The polycrystalline structure had an average size of 21 nm as determined by X-ray diffraction and transmission electron microscopy (high resolution). Antimicrobial sensitivity was observed in Capnocytophaga gingivalis (MIB/MIC 10–5 mg/mL), Eikenella corrodens (MIB 10 mg/mL), and Streptococcus sanguinis (MIB 20 mg/mL) at high concentrations of the MgO-NPs and at lower concentrations of the MgO-NPs in Actinomyces israelii (MIB 0.039 mg/mL), Fusobacterium nucleatum subsp. nucleatum (MIB/MIC 5–2.5 mg/mL), Porphyromonas gingivalis (MIB 20 mg/mL/MIC 2.5 mg/mL), Prevotella intermedia (MIB 0.625 mg/mL), Staphylococcus aureus (MIC 2.5 mg/mL), Streptococcus mutans (MIB 20 mg/mL/MIC 0.321 mg/mL), and Streptococcus sobrinus (MIB/MIC 5–2.5 mg/mL). (4) Conclusions: The MgO-NPs’ reported antibacterial properties in all oral biofilm strains were evaluated for potential use in dental applications.</jats:p>