Developing new materials capable of the safe and efficient removal of toxic substances has become a research hotspot in the field of materials science, as these toxic substances pose a serious threat to human health, both directly and indirectly. Covalent organic frameworks (COFs), as an emerging class of crystalline porous materials, have advantages such as large specific surface area, tunable pore size, designable structure, and good biocompatibility, which have been proven to be a superior adsorbent design platform for toxic substances capture. This review will summarize the synthesis methods of COFs and the properties and characteristics of typical toxicants, discuss the design strategies of COF-based adsorbents for the removal of toxic substances, and highlight the recent advancements in COF-based adsorbents as robust candidates for the efficient removal of various types of toxicants, such as animal toxins, microbial toxins, phytotoxins, environmental toxins,