The red algae Chondrophycus papillosus belongs to the genus Chondrophycus of family Rhodomelaceae, which is widely distributed in the offshore area of Guangdong and Hainan Island in China. In previous reports, only one linear diterpene, one steroid, three benzene derivatives, and sulfated xylomannans have been isolated from C. papillosus [1, 2]. Recently, in the course of our search for bioactive substances from Chinese marine alga, the EtOAc crude extract of C. papillosus displayed strong in vitro activities against tumor cell lines K562, SGC-7901, and SMMC-7721. Further investigation on the chemical constituents of C. papillosus resulted in the isolation and identification of nine compounds, including three aristolane sesquiterpenes 1–3, one snyderane sesquiterpene 4, three polybrominated indoles 5–7, one linear diterpene 8, and one cholesterol derivative 9. This paper describes the isolation, structure elucidation, and bioactivity evaluation of these compounds.