Stevia rebaudiana (Asteraceae), commonly known as candyleaf, sweetleaf, or sugarleaf, is a branched bushy shrub whose leaves are used as a natural sweetener owing to the high content of sweet diterpenes. As part of our ongoing work to identify structurally novel and bioactive natural products, phytochemical investigation of the ethanolic extract of S. rebaudiana leaves led to the isolation of one new labdane-type diterpene, 6-O-acetyl-(12R)-epiblumdane (1), and nine known terpenoids, including six diterpenes (2–6 and 10), two monoterpenes (7 and 8), and one triterpene (9). The structure of the new compound 1 was elucidated via analysis of one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry data, and its absolute configuration was established using electronic circular dichroism (ECD) calculations and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4 + probability analysis. The isolated compounds 1–10 were evaluated for their effects on glucose-stimulated insulin secretion in the INS-1 rat pancreatic β-cell line. The new compound 1, 6-O-acetyl-(12R)-epiblumdane, stimulated glucose-stimulated insulin secretion in INS-1 pancreatic β-cells without inducing cytotoxicity. Thus, 6-O-acetyl-(12R)-epiblumdane (1), an active compound derived from S. rebaudiana leaves, can be used as a potential therapeutic agent to prevent type 2 diabetes.