Morroniside (Mor) has been documented to has anti-diabetic activity. Nevertheless, the impact of Mor on the glucose metabolism and its underlying mechanism have never been elucidated. Here, we demonstrated that Mor improved the body weight, hyperglycemia, and insulin resistance in rat model of T2DM. Furthermore, Mor restrained renal glucose reabsorption of T2DM rats, accompanied by PPARδ upregulation and SGLT2 downregulation in renal tissues. The protein level of PPARδ was decreased, but SGLT2 was increased in HK-2 cells underwent high glucose stimulation. Mor enhanced PPARδ expression and inhibited SGLT2 expression in HK-2 cells under high glucose condition. PPARδ silencing rescued, but SGLT2 silencing reinforced the inhibitory effect of Mor on glucose uptake of HK-2 cells. In conclusions, Mor restrains renal glucose reabsorption to regulate glucose metabolism by regulating the PPARδ/SGLT2 signaling pathway, manifesting that Mor may be a promising therapeutic medicine for T2DM.