Abstract Circular RNAs (circRNAs) are a type of closed, long, non-coding RNAs, which have attracted significant attention in recent years. CircRNAs exhibit unique functions and are characterized by stable expression in various tissues across different species. Because the identification of circRNA in plant viroids in 1976, numerous studies have been conducted to elucidate its generation as well as expression under normal and disease conditions. The rapid development of research focused on the roles of circRNAs as biomarkers in diseases such as cancers has led to increased interests in evaluating the effects of toxicants on the human genetics from a toxicological perspective. Notably, increasing amounts of chemicals are generated in the environment; however, their toxic features and interactions with the human body, particularly from the epigenetic viewpoint, remain largely unknown. Considering the unique features of circRNAs as potential prognostic biomarkers as well as their roles in evaluating health risks following exposure to toxicants, the aim of this review was to assess the latest progress in the research concerning circRNA, to address the role of the circRNA-miRNA-mRNA axis in diseases and processes occurring after exposure to toxic compounds. Another goal was to identify the gaps in understanding the interactions between toxic compounds and circRNAs as potential biomarkers. The review presents general information about circRNA (ie, biogenesis and functions) and provides insights into newly discovered exosome-contained circRNA. The roles of circRNAs as potential biomarkers are also explored. A comprehensive review of the available literature on the role of circRNA in toxicological research (ie, chemical carcinogenesis, respiratory toxicology, neurotoxicology, and other unclassified toxicological categories) is included.