Introduction: We aimed to compare solubility between zinc oxide eugenol and zinc oxide eucalyptus. Methods: One hundred and twenty standardized plastic ring molds were constructed and filled with zinc oxide eugenol and zinc oxide eucalyptus. The specimens were allowed to dry for 24 hours and then weighed to the nearest 0.0001 g. Then divided randomly into three groups and immersed in distilled water for 1, 7, and 21 days. Then samples were removed from the solution and allowed to dry for 24 hours. Then they were weighed again, the percentage of weight loss was then determined as solubility. Data analyzed by two-way repeated measures ANOVA and the Tukey’s post-hoc test using MedCalc 20.104. Results: Zinc oxide eucalyptus solubility is more than zinc oxide eugenol. All tests of between-subjects effects and within-subjects effects showed statistically significant differences (P < 0.001). Conclusion: The 1st day results showed solubility of not more than 3% following storage in distilled water which meet the requirements of ISO 6876, where both zinc oxide-eugenol (ZOE) (0.05%) and zinc oxide eucalyptus (0.15%) satisfied these criteria.