Three rare and new 11,20-epoxy-ent-kaurane diterpenoids, named jianshirubesins D-F (1-3), along with one known analogue (4), were isolated from the aerial parts of Isodon rubescens. Their structures were established by analysis of spectroscopic data. Found in the MTT assay to evaluate the cytotoxicity of compounds 1, 2, and 4, only 1 could selectively inhibit certain cell lines from proliferating. In addition, a simple structure-activity relationship discussion might suggest a new bioactive moiety, different from the ${alpha}$,${eta}$-unsaturated ketone group.