Introduction Complex interactions between cariogenic bacteria and host factors modulate dental caries. , a gram-positive facultative anaerobe plays a prominent role in the initiation of caries. The ability of to adhere to salivary enamel pellicle results in an acidic local habitat for the organism. This leads to demineralization of the tooth and penetration of bacteria into the pulp leading to endodontic infections. an opportunistic pathogenis a gram-positive, facultative anaerobe implicated in secondary endodontic infections. This study aimed to evaluate the anti-bacterial efficacy of zirconium oxide nanoparticles (ZrO NPs) against and Materials and methods Standard and strains were subcultured at specific temperatures for 24 hours. was subcultured onto blood agar and colonies of were cultured on nutrient agar. The strains were tested for their sensitivity to ZrO NPs at various dilutions. The standard methods determined the minimum concentration of ZrO NPs to inhibit 99.9% growth of and . Results The zones of inhibition were compared with gentamicin as a control. ZrO NPs exhibited clear zones of inhibition of 12 mm and 15 mm at 100 mg/mL concentrations against and in the agar wells, respectively. Conclusion The present study concluded that ZrO NPs have potential anti-bacterial activity against both and .