Objectives: This study aimed to synthesize and evaluate the in vitro effects of varying concentrations (0.25%, 0.5%, and 1%) of calcium-substituted sodium trimetaphosphate (CaNaTMP) incorporated into 17.5% and 35% hydrogen peroxide (HP) whitening formulations on enamel color change, microhardness, morphology, surface roughness, mineral content, and transamelodentinal diffusion of HP. Materials and Methods: Enamel/dentin discs (N = 288) were allocated into eight groups according to the bleaching gel: (1) 35% HP; (2) 35% HP + 0.25% CaNaTMP; (3) 35% HP + 0.5% CaNaTMP; (4) 35% HP + 1% CaNaTMP; (5) 17.5% HP; (6) 17.5% HP + 0.25% CaNaTMP; (7) 17.5% HP + 0.5% CaNaTMP; and (8) 17.5% HP + 1% CaNaTMP. Gels were applied for 40 min across three weekly sessions. Evaluated parameters included total color change according to CIELab (Delta E), CIEDE2000 equation (Delta E-00), whiteness index (Delta WID), surface hardness (SH), surface roughness (Ra), enamel mineral content (g(HAp) x cm(-)(3) x mu m), and transamelodentinal of HP. Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) analyses were used to assess enamel surface characteristics. Data were analyzed using ANOVA and the Student-Newman-Keuls test (p < 0.05). Results: All bleaching gels caused significant color changes after treatment (p < 0.001), with similar Delta E, Delta E-00, and Delta WID values among them. Mineral loss (SH, g(HAp) x cm(-)(3) x mu m), Ra, and HP diffusion were highest with the 35% HP gel (p < 0.001) and lowest in groups containing CaNaTMP, particularly at 1% (p < 0.001). SEM/EDX analysis revealed no visible surface alterations in the 17.5% HP group, with prominent amorphous apatite precipitation in the 1% CaTMP-containing group. Incorporating CaNaTMP, particularly at 0.5% and 1%, into the 35% HP gel reduced surface changes. Conclusions: This study demonstrated that the addition of CaNaTMP to bleaching gels with 17.5% and 35% HP reduces mineral loss, changes in roughness, and surface morphology of enamel, as well as decreasing trans-amelodentinal diffusion of H2O2, without compromising the bleaching efficacy. The incorporation of 1% CaNaTMP was particularly more effective in protecting the dental enamel Clinical Relevance: The incorporation of CaNaTMP to 17.5% and 35% HP bleaching gels enhances safety and biocompatibility by reducing enamel damage. The lower HP concentration (17.5%) combined with 1% CaNaTMP provides a safer whitening option, maintaining effectiveness while minimizing adverse enamel changes, aimed at improving patient comfort during treatment.