The biological activities of the branch bark ethanol extract (BBEE) in the mulberry Morus alba L. were investigated. The determination of active component showed that the flavonoids, phenols, and saccharides are the major components of the ethanol extract. The BBEE had a good scavenging activity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with around 100 μg/mL of IC50 value. In vitro assay revealed that the BBEE strongly inhibited both α-glucosidase and sucrase activities whose IC50 values were 8.0 and 0.24 μg/mL, respectively. The kinetic analysis showed that the BBEE as a kind of α-glucosidase inhibitor characterized a competitive inhibition activity. Furthermore, the carbohydrate tolerance of the normal mice was obviously enhanced at 0.5 h (P<0.05) and 1.0 h (P<0.05) after the BBEE intragastric administration as compared to negative control. At 0.5, 1.0, 1.5, and 2.0 h after the intragastric administration with starch, the postprandial hyperglycemia of the type 2 diabetic mice can be significantly decreased (P<0.01) by supplying various concentrations of the BBEE (10–40 mg/kg body weight). Therefore, the BBEE could effectively inhibit the postprandial hyperglycemia as a novel α-glucosidase activity inhibitor for the diabetic therapy.