Trigeminal Neuralgia (TN) is one of the most commonly painful cranial neuralgia characterized by paroxysmal attacks as short lasting facial pain along the trigeminal nerve branches. The aim of the present study is to innovate a biochemical relationship between (melatonin, GALNT12 and Zn) and TN and also to examine the biochemical action of tegretol (carbamazepine) as a treatment on the above biochemical parameters. Blood samples were collected from fifty four (54) trigeminal neuralgia patients diagnosed by magnetic radiation image (MRI). Patients were classified into four groups: G3 (40- 70) years composed of (12) diagnosed male (without treatment), G4 (48- 75) years composed of (12) diagnosed female (without treatment), G5 (34- 76) years composed of (15) male under treatment with tegretol (200 mg /daily) and G6 (49-65) years composed of (15) female under treatment with tegretol (200 mg/ daily). Patients were compared with healthy subjects (have approximately the same range of age) as control groups: G1 composed of (15) males (43-70) years and G2 composed of (15) females (50-55) years. The present study is the first reporting that melatonin is a novel biochemical marker in Iraqi patients with TN (with significant and highly significant decrease in males and females respectively compared with healthy subjects). Also it is the first reporting that GALNT12 and Zn are novel biochemical markers in Iraqi patients with TN (with highly significant decrease in both genders compared with healthy subjects). The present study is the first highlighting and dealing with the biochemical action of tegretol (carbamazepine) on melatonin, GALNT12 and Zn by submitting unique and novel mechanisms. Finally the present study confirms the specific role of tegretol (carbamazepine) on postmenopausal women regarding melatonin, and GALNTI2 by focusing on its interaction with female sexual hormones.