Melanoidins, as macromolecular heterogeneous organic polymers, are produced from the Maillard reaction between amino and carbonyl groups during the thermal hydrolysis pretreatment (THP) of sludge. The brown color and recalcitrance of melanoidins pose a serious threat to wastewater treatment systems, such as invalidating UV disinfection and decreasing the efficiency of anaerobic digestion; thus, they have gradually received much concern in recent years. However, currently the study on THP-origin melanoidins is limited by a lack of reliable extraction and quantification methods. This paper presents a comprehensive review of the physical, chemical, and biological properties of melanoidins from different sources to fill the research gap on THP-origin melanoidins. The adverse effects of melanoidins on the management of wastewater and sludge are discussed, and for the first time, special attention is paid to the potential environmental hazards of THP-origin melanoidins to natural ecosystems. The removal technologies of melanoidins are summarized and compared as well. Finally, the suggested areas that future studies should focus on are provided. This review is dedicated to providing guidance on melanoidin research and management for the better development of the THP industry.