Background: Oral infections are commonly encountered among populations and frequently result in chronic inflammatory conditions that impact the dental structures (e.g., caries), the gingival tissues surrounding the dental elements (e.g., gingivitis and endodontic lesions), as well as the supporting structures of the teeth (e.g., periodontitis). Objectives: The objective of this study is to ascertain the minimum inhibitory concentrations of silica nanoparticles in order to evaluate the antibacterial efficacy of these nanoparticles against oral pathogens. Materials and Methods: A total of 100 clinical samples were collected from individuals suffering from diverse oral infections. They were diagnosed based on the culture and microscopic characteristics, as well as the diagnosis with Vitek2 device for the purpose of diagnosis for the level of species. Molecular identification of Viridians Streptococci was performed using PCR to detect the 16sRNA gene. The study also involved the synthesis of silica nanoparticles (SiNPs) using the sol-gel technique. Characterization of the SiNPs was conducted through X-ray diffraction (XRD), transmission electron microscopy (TEM), and field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FESEM-EDX). The minimum inhibitory concentration (MIC) of the SiNPs against viridans Streptococci was evaluated using a microdilution assay with the blue-resazurin staining method. The agar well diffusion technique was utilized to assess the antibacterial efficacy of biosynthesized silica nanoparticles against Viridans Streptococci in comparison to a standard antibiotic, utilizing the minimum inhibitory concentration (MIC) as a metric. Results: Fifty pathogenic bacterial strains were obtained from clinical specimens, with the genus Streptococcus comprising 27 of these isolates, which corresponds to 54% of the overall total, thereby constituting the highest proportion observed among all species. Molecular identification of Viridans Streptococci in this study, showed that 10/10(100%) isolates were PCR positive for 16sRNA gene has been applied to pathogenic viridians streptococcal only, which include S. mitis, S. oralis and S. sanguinis. Multidrug-resistant isolates showed significant resistance to various antibiotics, including Erythromycin, Cefotaxime, Cefepime, Ceftriaxone, and Penicillin. Clindamycin also showed resistance. Augmentin showed the highest antimicrobial activity, while Trimethoprim-sulfamethoxazole, Ampicillin, and Vancomycin showed commendable activity. The MIC for the synthesized silica nanoparticles against Viridans Streptococci was determined to be 3.13 mg/mL across all bacterial isolates. The study showed that the bio-synthesized silica nanoparticles had a higher inhibition than the standard antibiotic disc Vancomycin (VA) at a concentration of 3.13 mg/ml, as the average diameter of inhibition reached 26.2 mm, respectively. Conclusion: Silica nanoparticles demonstrated significant efficacy in combating Viridans Streptococci, which are implicated in the etiology of oral infections.