Objective <p>To evaluate the effect of adding bioactive glass (nBG) and hydroxyapatite (nHAp) nanoparticles to an experimental bleaching gel on 40% hydrogen peroxide (H₂O₂) diffusion into the pulp chamber, bleaching efficacy (BE), potential of hydrogen (pH) and its effects on enamel’s chemical, mechanical, and physical properties.</p> Materials and methods <p>Nanoparticles of nBG and nHAp were synthesized, characterized, and incorporated into a 40% H₂O₂ bleaching gel. Thirty premolars were divided into three groups (<i>n</i> = 10): (1) Control group = 40% H₂O₂ bleaching gel; (2) nBG group: 40% H₂O₂ bleaching gel + bioactive glass (Si: Ca: P); (3) nHAp group: 40% H₂O₂ bleaching gel + nano-hydroxyapatite. The H₂O₂ diffusion was measured by UV-Vis spectrophotometry, and BE was assessed by digital spectrophotometry (ΔE_ab,) before and after 7 days bleaching. The pH was measured at baseline and after 45&#xa0;min. To evaluate enamel surface alterations, 120 enamel blocks from 30 third molars were analyzed for their chemical (EDS, XRD and Raman), mechanical (microhardness, nanohardness and elastic modulus), and physical (roughness and optical profilometry) properties before bleaching treatment (BT) and after one-week treatment (AT). All data were subjected to statistical analysis (α = 0.05).</p> Results <p>The nBG and nHAp groups showed significantly lower H₂O₂ diffusion than the control group (<i>p</i> = 0.01), with no differences in BE (<i>p</i> &lt; 0.32). The initial pH of the nBG group was significantly different from the others (<i>p</i> = 0.01), but this difference was not maintained at 45&#xa0;min. The nHAp group presented higher Ca (<i>p</i> = 0.01) and P (<i>p</i> = 0.01) values and a greater hydroxyapatite peak intensity than other groups. A significant time-group interaction was observed for mechanical and physical properties (<i>p</i> = 0.01). While no BT differences were found, the values of these properties significantly increased for the nHAp group at AT.</p> Conclusion <p>Incorporating nBG and nHAp, into a 40% H₂O₂ bleaching gel significantly reduces H₂O₂ diffusion into the pulp chamber without compromising BE. Although both materials mitigate deleterious effect of tooth bleaching, nHAp demonstrates a superior performance in preventing demineralization.</p> Clinical relevance <p>The incorporation of nBG and nHAp into bleaching gels represents a promising approach for a safer in-office bleaching treatment.</p>