This study found that a single 15 Gy dose of gamma irradiation to the cranium of rats caused significant damage to parotid glands, including acinar vacuolization, fibrosis, and increased TGF-β expression. Oral administration of Nigella sativa oil (400 mg/kg) before and after irradiation preserved gland architecture, reduced fibrosis, and decreased TGF-β expression. These findings suggest NSO may be a useful radioprotective adjuvant for salivary glands during radiotherapy.