A dried infusion prepared from the aerial parts of Salvia circinata did not provoke acute toxicity in mice (LD50 > 5 g/kg). This infusion showed poor hypoglycemic and antihyperglycemic effects (100−570 mg/kg) when tested in normal and hyperglycemic mice using acute and oral glucose tolerance tests, respectively. However, this infusion possessed antihyperglycemic action in vivo during an oral sucrose tolerance test (31.6−316 mg/kg), suggesting the presence of α-glucosidase inhibitors in S. circinata. Fractionation of a nonpolar extract of the aerial parts of the plant yielded a new biflavone (1) and four new neoclerodane diterpenoid glucosides (2−5) along with the known compounds amarisolide (6), pedalitin (7), apigenin-7-O-β-Dglucoside (8), and the flavone 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy7-methoxy-4H-chromen-4-one (9). Compounds 1 and 6−9 were active against mammalian α-glucosidases; 6 and 7 were also active against a recombinant α-glucosidase from Ruminococcus obeum and reduced significantly the postprandial peak during an oral sucrose tolerance test in healthy mice, consistent with their α-glucosidase inhibitory activity. Molecular docking and dynamic studies revealed that compounds 6 and 7 might bind to α-glucosidases at the catalytic center of the enzyme.