A number of galectin protein family members have significant roles in promoting cancer and inflammation, some also indicate a role in regulating bone-remodeling, leading to bone loss. Galectins exhibit interactions with cell-surface glycans that can facilitate disease progression, for example by promoting metastasis in cancer. Designing small molecule compounds that target galectins and compete with their interactions toward endogenous carbohydrates is important in developing potential therapeutics, but is challenging due to characteristics of the carbohydrate-binding site of galectins. This presentation focuses on our structure-based design of small molecules that bind within the galectin carbohydrate-binding site, and thus have potential to reduce their lectin function within biological systems. Our approach to the design of compounds that target galectins includes X-ray crystallographic structure determination of galectins in complex with such blocking agents, giving insight into structural features that are important in the design of potent and selective inhibitors of galectins.