Chemical investigation of an ethanol extract of the sponge Agelas mauritiana led to the isolation and characterization of five new diterpene alkaloids, namely, (−)-8′-oxo-agelasine B (1), (+)-agelasine B (2), (+)-8′-oxo-agelasine C (3), agelasine V (4), and (+)-8′-oxo-agelasine E (5), along with two known compounds, (−)-8′-oxo-agelasine D (6), and agelasine D (7). The structures of these compounds were determined by interpretation of spectroscopic data and comparison with literature properties. Compounds 1 and 3–5 are the second example of 8′-oxo-agelasine analogs. Compounds 2 and 7 not only exhibited moderate cytotoxicity toward the cancer cell lines PC9, A549, HepG2, MCF-7, and U937 with IC₅₀ values of 4.49–14.41 μM, but also showed potent antibacterial activities against a panel of methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates with MIC₉₀ values of 1–8 μg mL⁻¹.