Osteoporosis is a degenerative disease characterized by decreased bone mass and destruction of bone microstructure. At present, previous studies have found that the structure and content of type Ⅰ collagen fibers are closely related to osteoporosis. However, there have been few studies on the prevention and treatment of osteoporosis using type Ⅰ collagen fibers as therapeutic targets. In this paper, the relationships between type Ⅰ collagen fibers and osteoporosis, biomechanics, bone matrix and bone strength are discussed. At the same time, the regulation of type Ⅰ collagen-related signaling pathways in osteoporosis is summarized, such as the signaling pathways of cathepsin K, transforming growth factor-β/Sma- and Mad-related protein, transforming growth factor-β/bone morphogenetic protein, c-jun N-terminal protein kinase and Wnt/β-catenin, in order to provide a new therapeutic direction for the prevention and treatment of osteoporosis.