Four new indole-C-mannopyranoside alkaloids, neopetrosins A-D (1-4), together with one new diamine alkaloid, haliclorensin D (6), were isolated from the marine sponge Neopetrosia chaliniformis collected off Xisha Island in the South China Sea. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, calculated electronic circular dichroism (ECD), and DP4+ probability analyses. Compounds 1, 2, and 4 exhibited in vivo hepatoprotective activity in a zebrafish model at a concentration of 20 μM.