Objective The aim of this study was to explore the reparative effects of glucosamine hydrochloride(GAH) and its derivatives on skeletal damage in zebrafish, and compare the preventive effects of GAH and alendronate sodium (AL), a drug known to be effective against osteoporosis. Methods Zebrafish embryos were exposed to various agents (GAH, glucose, mannitol, galactose, and acetylglucosamine) at the same concentration (0. 1%, 1 mg/ mL), and the mortality and phenotype were analyzed. Furthermore, a zebrafish model of osteoporosis induced by ferric ammonium citrate (FAC) was treated with the above agents to assess their reparative effects on the damaged skeleton examined using alizarin red and alcian blue staining. We also compared the preventive effects of GAH and AL on osteoporosis zebrafish.Results After treatment with GAH and its derivatives, the trend of their effects on embryonic development was glucose Conclusions Compared with other agents, GAH has an excellent reparative effect on zebrafish bone damage and a good preventive effect on osteoporosis in zebrafish. This study provides the foundation and approaches for screening of natural anti-osteoporosis drugs and product development using the zebrafish model.