Osteoporosis, characterized by low bone mineral density (BMD) and increased fracture risk, is a prevalent condition. Individuals with type 2 diabetes mellitus (T2DM) are at a higher risk of developing osteoporosis, necessitating the identification of biomarkers for early detection and management. This study aimed to investigate the potential of adiponectin and leptin levels as biomarkers for osteoporosis in T2DM patients. A total of 90 participants, including 30 healthy controls and 60 T2DM patients with osteoporosis, were enrolled. Dual-energy X-ray absorptiometry (DEXA) was utilized to assess bone mineral density. The demographic data were collected. Enzyme-linked immunosorbent assays (ELISA) were employed to measure adiponectin and leptin levels. The results demonstrated significantly lower adiponectin levels and higher leptin levels in T2DM patients with osteoporosis compared to the healthy control group. These findings suggest that adiponectin and leptin levels have the potential to serve as biomarkers for the diagnosis of osteoporosis and differentiation from healthy individuals in the context of T2DM.