Iron is one of the most common trace elements in natural water sources and an important component to living systems. The existence of iron may not only cause metallic flavor, it may also deeply impact health of human and animals by interacting with constituents in the related biological fluids such as saliva and milk. The overall goal of this study is to investigate the taste interaction between iron and sweeteners, and the interaction between iron and proteins in bovine milk and human saliva. Based on pairwise-ranking sensory test, we have found that sweetness of sweeteners was varied with different concentrations of minerals in water and with different types of sweeteners. Sweet-metallic taste interaction between sucrose and ferrous ions significantly (p<0.05) increased the acceptance of very hard water (3 mg Fe/L). The sweet-metallic interaction created a unique selection of the emotional term 'mild'. High iron concentration in bovine drinking water (2 mg Fe/L or higher), causing oxidative stress in dairy cattle, affected expression of both casein and whey proteins in the milk. Direct addition of iron above 5 mg Fe/L in processed whole commercial milk led to lipid oxidation during storage at 4°C. Oxidation level was positively associated with increasing concentration of added iron. Minerals (Mg, P, Na, K, Ca, Zn) in milk were not affected with the added iron in milk. Dietary supplementation with metal-binding protein significantly decreased (p<0.05) taste and smell abnormality score in cancer patients receiving chemotherapy, and this effect lasted at least 30 days after the treatment was ended. Although supplementation did not effectively reduce (p>0.05) the metallic taste intensity stimulated by ferrous sulfate solution (1 mg Fe/L), it significantly (p<0.05) decreased salivary Fe for both healthy subjects and cancer patients. The production of metallic taste perception both induced by chemotherapy and ferrous sulfate solution, might be associated with the decreased expression of low-abundance proteins (pH 5.5-8.5, MW 25-75kDa), which were mainly immune proteins in saliva. Supplementation may improve taste disorder by recovering low-abundance salivary proteins in cancer patients.