• Phanginin A inhibits gluconeogenesis in primary mouse hepatocytes. • Phanginin A increases hepatic SIK1 phosphorylation both in vitro and in vivo . • Activation of SIK1 increases PDE4 activity and suppresses the cAMP signaling pathway. • Activation of SIK1 inhibits gluconeogenesis by regulating the PDE4/cAMP/PKA/CREB pathway. • Phanginin A improves metabolic disorders in ob/ob mice.