Tehran University of Medical Sciences Journal of Food Safety and Hygiene 2476-3241 11 4 2026 01 01 304 325 David Anih Federal University Wukari Taraba, Nigeria Kayode Arowora Department of Biochemistry, Faculty of Biosciences, Federal University Wukari, Taraba, NIGERIA 2025 06 15 Mycotoxins secondary metabolites from fungi such as Aspergillus, Fusarium, and Penicillium are widespread food contaminants that pose health risks, particularly in undernourished populations. Nutritional deficiencies and gut microbiota imbalances further compound their toxicity. This review explores the biochemical interplay among gut microbiota, dietary nutrients, and mycotoxin detoxification. A systematic review was conducted following PRISMA 2020 guidelines. Peer reviewed studies published from January 2020 to March 2025 were retrieved from PubMed, Scopus, and Web of Science. Studies involving mycotoxins, gut microbiota, and nutritional modulation were included. Risk of bias was assessed using RoB 2 and PRISMA-ScR tools. Host phase I and II enzymes, along with microbial enzymatic systems, contribute to mycotoxin detoxification. Specific probiotic strains such as Lactobacillus and Bifidobacterium transform aflatoxins, ochratoxins, and  trichothecenes into less toxic forms. Micronutrients like vitamins A, C, E, selenium, and polyphenols modulate detox pathways and redox balance. Prebiotics and polyunsaturated fats support microbial profiles favoring detoxification. Synergistic interventions, such as probiotic–prebiotic systems (PPSP), show promise in enhancing host resilience. The proposed gut microbiota–nutrition mycotoxin triad offers a novel, integrative framework for mitigating foodborne toxicity. Understanding this biochemical cross-talk opens new avenues for precision nutrition, functional food development, and microbiome-targeted interventions aimed at reducing mycotoxin-induced health risks. https://jfsh.tums.ac.ir/index.php/jfsh/article/view/564