Introduction: Stichopus hermanii (SH), which contains various antioxidant agents, tends to protect oxidative stress caused by chronic cigarette smoking (CCS). This study, therefore, aims to investigate the protective effect of SH sup- plementation against CCS-induced oxidative stress in rat salivary glands. Methods: A total of 30 male Wistar rats, which were equally divided into the control (C), cigarette smoke (CS), and treatment (T) groups, were used to carry out this research. In T group, 17 mg/kg BW of SH was administered for 90 days. Their salivary glands were removed for oxidative stress marker analyses ie malondialdehyde (MDA) level, total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CAT) activity, with the data analyzed using one-way ANOVA and Tukey’s multiple comparison test to obtain a p-value of less than 0.05, which were considered statistically significant. Results: The re- sults showed that in the CS group oxidative stress occurred which was characterized by significantly increased MDA levels, reduced TAS, SOD and CAT activity. While the T group significantly decreased MDA levels, enhanced TAS, SOD and CAT activity. Conclusion: In conclusion, SH supplementation tends to prevent oxidative stress produced by CCS in rat salivary glands.