Cognition is a process in which the human brain receives external information, processes it, and transforms it into internal psychological activities to obtain or apply knowledge. Cognitive impairment is the impairment of one or more functions in memory, language, visual space, execution, calculation, and understanding, affecting an individual's daily or social ability. With the aging of the population, the incidence rate of cognitive impairment is increasing. Currently, biomarkers related to the cognitive impairment have become a research focus. Gut microbiota has emerged as a potential player in pathophysiology of cognitive impairment. Trimethylamine N-oxide (TMAO), the metabolite produced by gut microbiota, has mechanistic relevance to cognitive impairment. Therefore, the main goal of the present review is to provide the reader with potential mechanisms of TMAO and cognitive impairment. Although a link between TMAO and cognitive impairment is far from definitive, this review will serve as a call for research into this new area.