Substances such as choline, L-carnitine, and betaine contained in food can be converted into trimethylamine (TMA) under the action of gut microbiota. TMA can be easily absorbed by intestinal epithelial cells, transported to the liver through the portal circulation and then oxidized to trimethylamine-N-oxide (TMAO). The level of TMAO in plasma is closely related to the occurrence and development of cardiovascular diseases in humans. Therefore, gut-derived TMA is considered as a risk marker for cardiovascular disease. TMA is a metabolite of gut microbiota that get diet, gut microbiota, and cardiovascular disease closely linked, it provides a new target for the prevention and treatment of cardiovascular disease through diet and gut microbiota. Cardiovascular disease is considered to be a serious threat to human health, and analysis of the generation mechanism and influencing factors of gut-derived TMA could provide a reference for controlling gut-derived TMA and reducing cardiovascular disease incidence. The food sources of gut-derived TMA precursors and the gut microbes involved in the generation of TMA were described, and the metabolic pathways of TMA in body were systematically explained. For the control of gut-derived TMA, the aspects of reducing the intake of TMA precursors in food, reducing the proportion of gut microbiota that produce TMA, inhibiting TMA-producing enzymes, and intervening in the synthesis of gut-derived TMA were summarized. According to the probiotics and archaea intervention strategies with good application prospects, the current research results on the effects of probiotics and archaea on TMA were summarized, which provided possible directions for the prevention of cardiovascular diseases.