As a part of our ongoing search for bioactive constituents from natural Korean sources, the investigation of rhizomes of Acorus gramineus afforded five new lignans, named ligraminols A-E (1-5), together with seven known ones (6-12). The structures of 1-5 were determined by a combination of 1D and 2D NMR, HRMS, CD, and enzymatic hydrolysis. Compounds 1-12 were tested for their antiproliferative activities toward a panel of human-derived normal and cancer cell lines. Moreover, compounds 1-12 were evaluated for their inhibitory activities on nitric oxide production in an activated murine microglial cell line.