
Synthetic food dyes, including Indigo Carmine (E132), Brown HT (E155), Quinoline Yellow (E104), and Carmoisine (E122), are extensively utilized due to their chromatic stability, water solubility, and compatibility with processed food matrices. While regulatory bodies have approved their use, increasing experimental evidence suggests that the molecular structures of these dyes influence not only their color properties but also their interactions with biological macromolecules, toxicological profiles, and analytical detectability. This systematic review critically synthesizes literature published between 2010 and 2025 to elucidate structure–interaction–detection relationships for these four dyes. Following PRISMA 2020 guidelines, 105 eligible studies were analyzed, encompassing toxicological outcomes, protein and DNA binding mechanisms, sensor technologies, and validated analytical methods. Indigo Carmine and Carmoisine demonstrate a significant affinity for serum albumins and nucleic acids through hydrophobic, π–π stacking, and electrostatic interactions.