There is an urgent need to address food safety concerns associated with multiple Maillard reaction‒derived chemical contaminants, such as acrylamide, heterocyclic aromatic amines, advanced glycation end products, and 5-hydroxymethylfurfural, which are present in processed foods. Current studies have focused on single contaminant generated by the Maillard reaction
however, there is a dearth of information regarding the interactions of multiple contaminants and their joint control methods. This review article comprehensively summarizes the state-of-the-art progress in the simultaneous analysis, coformation, joint hazardous control, and risk assessment of multiple food processing contaminants generated by the Maillard reaction. The Maillard reaction is associated with caramelization, lipid oxidation, protein oxidation, and ascorbic acid browning reactions. Mass spectrometry‒based chromatography is currently the preferred method for the simultaneous quantification of multiple contaminants, with metabolomics and indirect detection methodologies providing new insights. Mitigation strategies for multiple contaminants include optimizing pretreatment, introducing exogenous additives, regulating processing parameters, and utilizing emerging technologies. Limited animal studies on the metabolism of various contaminants have yielded diverse results, guided by biomarkers for deep understanding. Integrated risk assessment should be conducted to quantify multihazard health impacts. In future research, a unique framework should be developed for assessing multiple contaminants, characterizing their metabolic profiles, and optimizing control measures for Maillard reaction‒derived contaminants.