Bone diseases encompass congenital skeletal disorders and metabolic conditions such as osteoporosis, the incidence of which is increasing worldwide with aging populations. Glycosaminoglycans (GAGs), including chondroitin sulfate (CS) and heparan sulfate, are major components of the bone extracellular matrix and play essential roles in skeletal development and bone homeostasis. Mutations in genes encoding GAG biosynthetic enzymes have been linked to various skeletal dysplasias. Both quantitative and qualitative alterations in GAG structure critically influence bone remodeling by regulating osteoblast and osteoclast activities. Notably, imbalanced CS sulfation contributes to hereditary osteosclerosis, whereas the highly sulfated CS-E subtype mediates estrogen-induced bone formation and suppresses osteoclast differentiation. Excessive GAG accumulation may also induce ectopic ossification under pathological conditions. Collectively, these findings underscore the importance of tightly regulated GAG biosynthesis and degradation in maintaining bone integrity. Glycobiological approaches may help elucidate the molecular mechanisms underlying metabolic bone diseases and rare skeletal disorders. Targeting enzymes involved in GAG metabolism represents a promising strategy for glycan-based therapeutic development.