Aaptaminoids are a unique family of marine alkaloids bearing a benzo[de][1,6]‐naphthyridine core. This work describes the first total synthesis of suberitines A–D (1–4), four typical dimeric natural aaptaminoids, employing a step‐saving bidirectional strategy. Key methods applied in the total synthesis include a cationic cascade to construct the bis‐isoquinoline(s) with Hendrickson reagent‐mediated Friedel‐Crafts‐type cyclization and eliminative aromatization, and a Bronsted acid‐promoted Vilsmeier cyclization to generate the naphthyridine(s). The conditionally tunable PIDA‐mediated oxidative dearomatization and subsequent methanolysis or hydrolysis successfully served as a powerful biomimetic tool to elaborate the essential oxygenated functionalities of suberitines A–D (1–4) in proper solvent‐combinations at the final stage of total synthesis. The biomimetic proposal employed in the late‐stage redox interchanges of related natural products was eventually supported by the isolation of synthetic intermediate 23 a as a natural product from the same natural source. Biological screening revealed that five of the synthetic samples including two natural suberitines and three full‐skeleton natural product‐like intermediates exhibited low micromolar inhibitory activities against the growth of cancer cell line K562.