Summary Glycyrrhetic acid diglycosides 2 and 46 ,, with respectively β- d --glucuronopyranosyl-(1→3)-β- d --glucopyranose, -(1→6)-α- d --glucopyranose, -(1→6)-β- d --glucopyranose, -(1→6)-β- d --galactopyranose, and β- d --galacturonopyranosyl-(→2)-β- d --glucopyranose as sugar components at the O --3 positions on the aglycons, were synthesized. In vitro cytoprotective activities, against CCl 4 --induced hepatic injury, of the synthetic diglycosides, methyl β- d --glucuronopyranosyl-(1→4)-α- d --glucopyranosyl- d --glycyrrhetinate 3 a and methyl esters 5 a and 3 ( (the precursors of 6 a and 4 r respectively) were compared with those of glycyrrhizin 1 and β- d --glucuronopyranosyl-(1→2)-β- d --glucopyranosyl-glycyrrhetic acid 2 .. Of the glycosides 4 , and, and 5 ,, with β- d --glucuronopyranosyl-glucopyranose as the sugar component, 6 a and 4 w were as cytoprotective as 1 and 2 ,, whereas 5 s showed no remarkable activity. From stereomodels of the glycosides these differences in activity were inferred to be due to the stereochemistries of the terminal β- d --glucuronopyranoses in the molecules. Glycoside 6 ,, in which the terminal β- d --glucuronopyranose of 2 was replaced by β- d --galacturonopyranose, was as potent as 2 .. Further, it was confirmed that a free COOH group on the E ring of aglycon was essential for the activity.