OBJECTIVE: This study aimed to assess if oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage. METHODS: Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + HO gavage (control) ( = 4); 15 Gy RT + HO gavage ( = 12); sham RT + NSO gavage ( = 12); and 15 Gy RT + NSO gavage ( = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment. RESULTS: All mice in the sham RT + HO gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + HO compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g ( < .001). Salivary output showed significant decline in RT + HO gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + HO gavage group did not recover as effectively. CONCLUSION: NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells. LEVEL OF EVIDENCE: Not applicable.