Traditional Chinese medicine (TCM) can help prevent or treat diseases; however, there are few studies on the active substances of TCM. For example, Lycium barbarumL. has been proven to be effective in treating osteoporosis for thousands of years, but its active substance remains to be unknown. Prompted by the efforts to modernize TCM, the present study focused on the novel active substance of Lycium barbarumL. to reinforce kidney essence to produce bone marrow. Illumina deep sequencing analysis and stem-loop polymerase chain reaction (PCR) assay revealed that miR162a, a Lycium barbarumL.-derived microRNA, can pass through the gastrointestinal tract to target the bone marrow in mice. Immunofluorescence staining showed that miR162awas absorbed through systemic RNA interference defective transmembrane family member 1 (SIDT1) in the stomach. Bioinformatics prediction and luciferase reporter assay identified that miR162atargeted nuclear receptor corepressor(NcoR). Alizarin red staining and micro-computed tomography (microCT) confirmed that miR162apromoted osteogenic differentiation in bone marrow mesenchymal stem cells, zebrafish, and a mouse model of osteoporosis. In addition, transgenic Nicotiana benthamiana(N. benthamiana) leaves overexpressing miR162awere developed by agrobacterium infiltration method. microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N. benthamianaleaves effectively protected against osteoporosis in mice. Our study mechanistically explains how Lycium barbarumL. improves osteoporosis and supports that Lycium barbarumL. reinforces kidney essence, thereby strengthening the bone. miR162aexpressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.