Purpose: To investigate the influence of vitamin K2 on bone mineral density, bone metabolism and serum tissue protease K (cathepsin K) in female patients with osteoporosis. Method: A total of 210 osteoporosis patients in Affiliated Hospital of Nanjing University of Chinese Medicine who met the inclusion criteria were selected from January 2017 to January 2018. The patients were randomly divided into vitamin K2 group, strontium renate group and blank control group (70 patients/group). Strontium ranelate group was orally given 2 g of strontium ranelate daily, while vitamin K2 group received 15 mg of Gulikang capsule 3 times a day. Bone mineral density (BMD) and serum osteocalcin (BGP), β-collagen degradation product (β-crosslaps), type I procollagen amino terminal propeptide (PINP), cathepsin K (cathe K) and TRAP were measured prior to drug treatment, and six months after surgery, using standard procedures. Results: Relative to the blank control, hip and lumbar spine density of vitamin K2 and strontium ranelate groups increased to varying degrees. Strontium ranelate group had significantly higher bone mineral density (BMD) than any other groups (p < 0.05), and also had the lowest osteoclast activity (β-crosslaps and TRAP) and the highest osteogenic activity (BGP and PINP). On the other hand, osteoclast and osteogenic activities increased significantly (p < 0.05) in the vitamin K2 group. Conclusion: Appropriate vitamin K2 treatment improves BMD in the hip and waist of women with osteoporosis by promoting osteogenic activity, and by reducing osteoclast activity and cathepsin K expression.