Osteoporosis is a progressive bone disease that leads to reduced bone mass and increased fracture risk, especially in postmenopausal women. Often developing silently, it is usually diagnosed only after fractures occur. Preptin, a peptide co-secreted with insulin, has recently been identified as a potential biomarker for bone health. This study aimed to measure preptin levels in the serum of osteoporosis patients in Mosul and explore risk factors such as age, sex, marital status, vitamin D3 and calcium deficiencies, and oxidative stress markers. The study included 100 newly diagnosed patients (75 women, 25 men) and matched healthy controls. Preptin levels were measured using ELISA, and additional biochemical markers like calcium, vitamin D3, glutathione, malondialdehyde, and oxidative stress indicators were assessed. The results showed significantly lower preptin levels in osteoporosis patients, particularly in women, with associations to vitamin D3 and calcium deficiencies. This suggests preptin could be an important early biomarker for osteoporosis.