This paper summarizes the guidance provided by quantum chemical calculations to the biomimetic syntheses of polycyclic marine furanocembrane derivatives. Polycyclic furanocembrane derivatives are a group of structurally complex and biologically important marine natural products isolated from marine corals. Their syntheses are challenging due to their structural complexity. Biomimetic synthetic proposals have been made and some verified via chemical synthesis. Computational chemistry can support these biomimetic syntheses. Hence, here we describe the synthetic and computational attempts we have made in the biomimetic syntheses of polycyclic furanocembrane derivatives, including intricarene, bielschowskysin, providencin and plumarellide.