Covering: up to February 2022Naturally occurring dimeric molecules attract considerable attention from both chemists and biologists. The methylene-bridged dimers with one-carbon (C1) unit in biosynthesis, which are a small class of structurally diverse natural products, are found in plants, microorganisms, and marine bryozoan. Some individual dimers showed more significant biological activities than the corresponding monomers. Focusing on these dimers with a methylene linker, we here reviewed associated progress in the isolation, biological activity, chemical synthesis, and the proposed dimerization mechanism. The structural characteristics of the monomeric substrates are summarized, which indicated that most of these dimers might be formed through nonenzymatic dimerization involving a strong electrophilic C1 unit such as formaldehyde. This kind of dimerization is an effective synthetic strategy for the discovery of new biologically active compounds.