Background: Mineral trioxide aggregate (MTA), a calcium silicate–based cement introduced in 1993, is widely used in vital pulp therapy due to its excellent sealing ability, biocompatibility, and low cytotoxicity. This study added propolis (known for its antibacterial activity) and ozonated water to MTA to evaluate their effects on its physical and mechanical properties. Methods: Three experimental groups (n = 18 each) were created by mixing MTA with distilled water (control), propolis, or ozonated distilled water. Initial and final setting times were measured, Vickers microhardness was recorded at 1, 3, 7, and 28 days, and compressive strength was evaluated on day 28. Surface morphology and elemental composition were analyzed using Field Emission Scanning Electron Microscopy/Energy-Dispersive X-ray Spectroscopy (FE-SEM/EDS). Data were analyzed with repeated measures Analysis of Variance (ANOVA) or Friedman tests for intra-group comparisons and using one-way ANOVA or Kruskal-Wallis tests for inter-group comparisons (p < 0.05). Results: Propolis significantly prolonged both the initial (6 min) and final setting times (238.611 ± 4.804 min) compared with the other groups (p < 0.001), whereas ozonated water yielded values similar to those of the control. The compressive strength of the MTA + propolis group (30.749 ± 3.374 MPa) was significantly lower than that of the other groups (p < 0.001). Microhardness increased over time in all groups (p < 0.001), but the values in the propolis group remained consistently lower at all measurement points (p < 0.001). FE-SEM analyses revealed that crystalline formation was preserved in all groups, but samples with added propolis exhibited a film-like layer partially covering the surface. Conclusions: The addition of propolis adversely affected the physical and mechanical properties of MTA, whereas ozonated distilled water preserved its structural integrity, suggesting that ozonated water may be a safe alternative liquid for the clinical modification of MTA.