Glycogen synthase kinase-3β (GSK-3β) is a conserved serine/threonine kinase that participates in the transmission of multiple signaling pathways and plays an important role in the occurrence and development of human diseases, such as metabolic diseases, neurological diseases and cancer, making it to be a potential and promising drug target. To date, copious GSK-3β inhibitors have been synthesized, but only few have entered clinical trials. Most of them exerts poor selectivity, concomitant off-target effects and side effects. This review summarizes the structural characteristics, biological functions and relationship with diseases of GSK-3β, as well as the selectivity profile and therapeutic potential of different categories of GSK-3β inhibitors. Strategies for increasing selectivity and reducing adverse effects are proposed for the future design of GSK-3β inhibitors.