New carabrane-type sesquiterpene lactones, curcumenolactones A, B, and C, were isolated from the 80% aqueous acetone extract of Zedoariae Rhizoma (Zingiberaceae), together with 41 sesquiterpenes and two diarylheptanoids. The absolute stereostructures of curcumenolactones A, B, and C were determined on the basis of physicochemical evidence, which included nuclear Overhauser effect (NOE) and circular dichroic (CD) spectroscopic analyses. Curcumenone, a principal carabrane-type sesquiterpene from Zedoariae Rhizoma, was found to show potent protective effect on D-galactosamine/lipopolysaccharide-induced acute liver injury in mice. In addition, curcumenolactones A and B and the other constituents showed protective effect on D-galactosamine-induced cytotoxicity in primary cultured rat hepatocytes.