The petroleum ether extract of Panax ginseng showed a significant inhibition of the diacylglycerol acyltransferase (DGAT) enzyme from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of two new polyacetylenic compounds, (9R,10S)-epoxyheptadecan-4,6-diyn-3-one (1) and 1-methoxy-(9R,10S)-epoxyheptadecan-4,6-diyn-3-one (2). Their chemical structures were elucidated on the basis of spectroscopic evidence and asymmetric synthesis. IC50 values of 9 μg/mL (1) and 32 μg/ml (2) were obtained.