Defending parotid gland against deleterious effects of hypothyroidism may be conquered by using herbal substances such as propolis or Nigella sativa oil. Aim of work: This study was theorized to evaluate probolis versus NsO in amelioration of hazards of Propylthiouracil-induced Hypothyroidism on parotid gland; amending the influences of apoptosis and oxidative stress Material and Methods: 30 male rats were utilized; group I (control), group II (sham control), group III (PTU-induced hypothyrodism), Group IV: (PTU + probolis), Group V: (PTU + NsO), Histo-pathological; H&E, masson trichrome, toluidine blue, α-SMA were performed. MDA and GPx, molecular studies for Bcl2, Bax, caspase and p53 were evaluated. Results: severe pathological alterations in group III; irregular outline, shrunken acini with darkly stained pyknotic nuclei, interstitial exudate, inflammatory infiltrates, and extravasated blood were encountered. Marked increment in mean values of collagen, mast cells, SMA, P53, Bax and caspase. Surprisingly, Nso and probolis ameliorated these deleterious changes in an outstanding manner.