Background <p>Considering the efficacy of antimicrobial photodynamic therapy (PDT) in inactivating bacteria, this study reports that zinc hydroxide chloride nanosheets (ZHC-NSs) are useful for this purpose.</p> Materials &amp; methods <p>The characterization of ZHC-NSs was performed using microscopic and spectroscopic techniques. The irritation test, acute toxicity test, and genotoxicity test of ZHC-NSs were evaluated and their effects on human pulp fibroblast cells (HPFC) viability, intracellular reactive oxygen species (ROS) levels, and antibacterial activity of ZHC-NSs (1–8 mg ml⁻¹) alone or in light conditions were investigated.</p> Results <p>The ZHC-NSs structure&#xa0;showed&#xa0;a crystalline form and their sheets’ thickness had an average size of 129.6 ± 19.50 nm. ZHC-NSs did not severely damage internal organs and were&#xa0;not genotoxic. The cytotoxic effect of ZHC-NSs on HPFC was concentration-dependent so that ZHC-NSs at higher concentrations (4 and 8 mg ml⁻¹) killed half of the HPFC cells. When ZHC-NSs were used in combination with a 980 nm diode laser, namely ZHC-NS^©, ROS production increased and led to enhanced antibacterial activity against <i>Streptococcus</i>&#xa0;<i>mutans</i> in planktonic and biofilm form. A statistically significant difference was found between ZHC-NSs without laser irradiation and photoexcited ZHC-NSs.</p> Conclusion <p>ZHC-NSs^© with the potential ability to produce ROS could be effective in complementary treatment against <i>S. mutans</i>.</p>