Two unprecedented 4/9/5-membered ring sesquiterpene-indole alkaloids, amomaxyz A (1) and B (2), along with one known compound caryolane-1,9β-diol (3), were isolated from the fruit of Amomum maximum Roxb. Their structures and absolute configurations were elucidated through comprehensive spectroscopic analyses, including NMR, electronic circular dichroism (ECD), X-ray single-crystal diffraction, and DP4 probability analysis of calculated NMR data. Biological evaluation revealed distinct anti-inflammatory and anticancer activities. 1 demonstrated dose-dependent anti-inflammatory activity by suppressing NO release in LPS/IFN-γ-activated RAW264.7 macrophages (25.9% at 10 μM, 29.9% at 20 μM; P < 0.01), while 2 and 3 exhibited weaker effects. Moreover, 1 (IC50 = 30.62 μM) and 2 (IC50 = 23.43 μM) showed moderate inhibitory effects against HepG2 cells, which reveals the potential of their biological activity.