The crude dichloromethane extracts of the marine brown algae Cystophora monilifera and Cystophora subfarcinata were subjected to phytochemical profiling. This enabled the structures of both new and known phloroglucinols to be dereplicated and proposed using HPLC-NMR and HPLC-MS. Subsequent isolation confirmed the presence of four new and eight previously reported compounds. Five of the isolated phloroglucinols displayed selective antimicrobial activity.