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Abstract Maillard reaction (MR) is a cascade of complex interactions between reducing sugars and amine groups in food processing and storage. It produces a variety of volatile compound, nonenzymatic intermediates, and high molecular weight melanoidin contributing improved aroma, color, flavor, and antioxidant properties to the final food products. When uncontrolled, it can produce some harmful derivatives such as acrylamide, heterocyclic amine, advanced glycation end Products (AGEs), and other substances that can be detrimental to human health leading to cancer and chronic diseases. Herein, we reviewed the MR leading to different MRPs and factors affecting the MR and MRPs, their application in food model systems, their biological activities, and the formation mechanism and effective inhibition methods of common harmful MRPs. The updated overview can be useful to explore the rational use of MR, which can ameliorate its positive biological features with reduced adverse effects.