Six new angucycline derivatives, named monacycliones G-K (1-5) and ent-gephyromycin A (6), as well as three known ones (7-9) were discovered from the marine sediment-derived actinomycete Streptomyces sp. HDN15129 guided by Global Natural Products Social (GNPS) molecular networking. Structures including absolute configurations were elucidated by extensive NMR, MS, and ECD analyses. Among them, monacyclione G (1) possesses a unique scaffold featuring a xanthone core linked to the aminodeoxysugar ossamine, and monacycliones H-J (2-4) are rare examples of natural angucyclines with an S-methyl group. Monacycliones I and J (3 and 4) showed cytotoxic activity against multiple human cancer cell lines, with IC values ranging from 3.5 to 10 μM.