Objective To investigate the preventive effects and potential mechanisms of Shenxiankang in chronic kidney disease-mineral and bone disorder ( CKD-MBD). Methods A rat model of CKD-MBD was established. Serum creatinine(Scr) and blood urea nitrogen(BUN) were measured. Serum levels of bone alkaline phosphatase(BALP), intact parathyroid hormone ( iPTH), vitamin D3 (VD3 ), cartilage oligomeric matrix protein (COMP), fibroblast growth factor 23 ( FGF23), klotho, and fibroblast growth factor receptor 1 ( FGFR1) were determined by ELISA. Histopathological changes in renal tissues were examined using hematoxylin-eosin ( HE),Masson, and picrosirius red staining. Femoral tissue morphology was assessed by HE, Masson, and tartrate-resistant acid phosphatase staining, while femoral structural parameters were evaluated using micro-computed tomography. The mRNA and protein expression levels of COMP, FGF23, klotho, and FGFR1 in renal tissues were analyzed by quantitative real-time reverse transcription PCR(RT-qPCR) and Western Blot. In addition, the expression of these molecules in renal and bone tissues was examined by immunohistochemistry. Results Compared with CKD-MBD group rats, Shenxiankang treatment significantly reduced serum creatinine, blood urea nitrogen, bone alkaline phosphatase, intact parathyroid hormone, COMP, and FGF23 (P<0. 01, P<0. 05), while significantly increasing serum VD3 , klotho, and FGFR1 (P<0. 01). Shenxiankang also alleviated renal injury, collagen fiber deposition,and inflammatory infiltration and improved osteoporosis and bone metabolic abnormalities. Furthermore, Shenxiankang downregulated mRNA and protein expression of COMP and FGF23 in renal tissues (P<0. 01), while upregulating mRNA and protein expression of klotho and FGFR1 ( P<0. 01, P<0. 05). Immunohistochemical findings were consistent with these molecular result. Conclusions Shenxiankang effectively prevents and treats renal and skeletal abnormalities in CKD-MBD rats. Its therapeutic effects may be associated with downregulation of COMP and modulation of the FGF23-klotho signaling axis.