This study was carried out to extract ginsenosides in by-products from honeyed red ginseng. Response surface methodology (RSM) was used to optimize the extraction conditions. Based on D-optimal design, independent variables were ethanol (extraction solvent) concentration (30-90%, v/v), extraction temperature (25-70oC), and extraction time (5-11 h). Extraction yield (Y1) and total ginsenosides (Y2) in the extract were analyzed as dependent variables. Results found that extraction yield increased with increasing extraction temperature and time, whereas it was decreased with increasing ethanol concentration. Similar trends were found for the content of ginsenosides in the extracts, except for ethanol concentration, which was increased with increasing ethanol concentration. Regression equations derived from RSM were suggested to coincide well with the results from the experiments. The optimal extraction conditions for extraction yield and total ginsenosides were an extraction temperature of 56.94oC, ethanol concentration of 57.90%, and extraction time of 11 h. Under these conditions, extraction yield and total ginsenoside contents were predicted to be 84.52% and 9.54 mg/g, respectively.