Ginsenoside is an important class of saponin biosurfactant that is derived from ginseng. The interactions between ginsenoside Ro, Rb-1, and Rg(1) with saikosaponin a (SSa) were explored using multiscale methods. The order of interaction strength was found to be Ro > Rb-1 > Rg(1). Ro markedly increased the solubility of SSa; however, Rb-1 could only disperse SSa solid in aqueous medium. No significant interaction was observed between Rg(1) and SSa. Ro formed vesicles in aqueous medium while Rb-1 and Rg(1) formed spherical micelles. The differences in the available surface area of the aggregates appear to have some influence on the interactions between ginsenoside and SSa. However, more important effects are related to their chemical structures and interaction energy. According to the molecular simulation results, glucuronic acid linked to Ro molecules significantly reduced the potential energy through its strong electrical attraction to SSa, which contributed greatly to the strong compatibility between them. The greater number of sugars in Rbi, as compared to Rg(1), created more binding sites with SSa, thus resulting in stronger interaction between Rb-1 with SSa than between Rg(1) and SSa. Spherical and worm-like micelles were found to be formed by Rb-1 and SSa molecules. This was different from Ro and SSa, which formed vesicles. The formation of worm-like micelles was through the fusion and modification of small spherical micelles. These results may guide in expanding the applications of ginsenoside. (C) 2013 Elsevier Inc. All rights reserved.