The salt-inducible kinase (SIK) family includes three isoforms, SIK1, SIK2 and SIK3, which are the main regulators of physiological and pathological processes and participate in the regulation of glucose and lipid metabolism, tumor, inflammation, depression, sleep-wake and circadian rhythm. SIK inhibitor has become a candidate drug for the treatment of a variety of diseases, and is especially expected to become a potential new drug for the treatment of nervous system diseases, such as sleep disorders, circadian rhythm disorders, and depression. This review summarizes the regulation and mechanism of three isoforms of SIK and their upstream and downstream signaling pathways in the above physiological and pathological processes. It also reviews the recentstudies of SIK inhibitors.