The antioxidant activity of lemon balm (Melissa officinalis) essential oil (LBEO) on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and its hypoglycaemic effect in db/db mice were investigated. LBEO scavenged 97 % of DPPH radicals at a 270-fold dilution. Mice administered LBEO (0·015 mg/d) for 6 weeks showed significantly reduced blood glucose (65 %; P < 0·05) and TAG concentrations, improved glucose tolerance, as assessed by an oral glucose tolerance test, and significantly higher serum insulin levels, compared with the control group. The hypoglycaemic mechanism of LBEO was further explored via gene and protein expression analyses using RT-PCR and Western blotting, respectively. Among all glucose metabolism-related genes studied, hepatic glucokinase and GLUT4, as well as adipocyte GLUT4, PPAR-γ, PPAR-α and SREBP-1c expression, were significantly up-regulated, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression was down-regulated in the livers of the LBEO group. The results further suggest that LBEO administered at low concentrations is an efficient hypoglycaemic agent, probably due to enhanced glucose uptake and metabolism in the liver and adipose tissue and the inhibition of gluconeogenesis in the liver.