In recent years, L-asparaginase has garnered substantial attention worldwide due to its versatile applications in the mitigation of acrylamide levels without compromising the final product's flavor, texture, or taste in several food commodities to protect the health of people worldwide. L-asparaginase is distributed across animals, plants, and microorganisms, including bacteria, archaea, yeast, and fungi. Among these, microorganisms are particularly noted as a crucial source of this enzyme; however, cost-effective production remains a major challenge. Therefore, researchers are interested in the commercial production of L-asparaginase using cost-effective feedstocks. In this context, bioprospecting for microbial strains capable of producing L-asparaginase from abundantly available waste materials through fermentation is emerging as a promising strategy. Using renewable waste as a substrates that contain ample carbon and nitrogen sources offers a sustainable and economical solution for the commercial production of L-asparaginase. This review aims to systematically analyze and provide a comprehensive overview of scientific research related to the sustainable production of L-asparaginase from waste materials through microbial fermentation processes. Moreover, it also consolidates current knowledge on the role of L-asparaginase in reducing acrylamide, generated through the Maillard reaction, in thermally processed food. Furthermore, outlines factors influencing acrylamide reduction through microbial L-asparaginase in the food industry have been emphasized. Additionally, it emphasizes the role of artificial intelligence (AI) in optimizing and monitoring L-asparaginase production. Moreover, the review highlights key challenges associated with the commercial application of L-asparaginase and discusses prospects within the food industry. In conclusion, harnessing agri-food waste as a microbial growth substrate not only reduces production costs but also addresses waste management challenges and contributes to environmental sustainability, aligning with the UN Sustainable Development Goals (SDGs).