Melocochines A (1) and B (2), one pair of epimers with an unprecedented skeleton, were isolated from Melodinus cochinchinensis. Their structures and absolute configurations were established by a combination of MS, NMR, and single-crystal X-ray diffraction analyses. Compounds 1 and 2 represent a class of novel alkaloids, characterized by a rare 1H-benzo[b]azepane ring system within monoterpenoid indole alkaloid categories. Compounds 1 and 2 enhanced lysosomal biogenesis with LysoTracker staining intensities of 139.7% and 119.0%, respectively.