This review explores the intricate interactions between iron (Fe), calcium (Ca), magnesium (Mg), and trace elements (Cu, Zn, Pb, Cd, Hg, Ni) in the human body. Iron is a fundamental element essential for life, playing crucial roles in oxygen transport, DNA synthesis, and various biological processes. The balance of Fe is tightly regulated by proteins such as DMT1, FPN1, Trf, and TrfR, with hepcidin coordinating ferroxidases like DCYTB, Cp, and hephaestin to ensure efficient Fe acquisition and utilization. The review highlights how these elements share some proteins involved in Fe absorption and transport. For instance, Cu and Cd can inhibit Fe absorption, while excess Fe can antagonize Cu metabolism and reduce Cp levels. Excessive Fe can also hinder Zn absorption, and Trf can bind to both Zn and Ni. Ca can inhibit DMT1, reducing Fe absorption, and low Mg concentrations can exacerbate Fe deficiency. Pb competitively inhibits Fe distribution, and elevated Cd absorption reduces Fe uptake. Exposure to Hg is associated with higher ferritin concentrations, and Ni alters intracellular Fe metabolism. The historical context of Fe's impact on human health is discussed, from ancient civilizations to modern times. The review aims to evaluate the biological interactions of Ca, Mg, and selected trace elements with Fe and their roles in certain diseases. Understanding these interactions is crucial for developing strategies to mitigate the adverse effects of these elements on health.This review explores the intricate interactions between iron (Fe), calcium (Ca), magnesium (Mg), and trace elements (Cu, Zn, Pb, Cd, Hg, Ni) in the human body. Iron is a fundamental element essential for life, playing crucial roles in oxygen transport, DNA synthesis, and various biological processes. The balance of Fe is tightly regulated by proteins such as DMT1, FPN1, Trf, and TrfR, with hepcidin coordinating ferroxidases like DCYTB, Cp, and hephaestin to ensure efficient Fe acquisition and utilization. The review highlights how these elements share some proteins involved in Fe absorption and transport. For instance, Cu and Cd can inhibit Fe absorption, while excess Fe can antagonize Cu metabolism and reduce Cp levels. Excessive Fe can also hinder Zn absorption, and Trf can bind to both Zn and Ni. Ca can inhibit DMT1, reducing Fe absorption, and low Mg concentrations can exacerbate Fe deficiency. Pb competitively inhibits Fe distribution, and elevated Cd absorption reduces Fe uptake. Exposure to Hg is associated with higher ferritin concentrations, and Ni alters intracellular Fe metabolism. The historical context of Fe's impact on human health is discussed, from ancient civilizations to modern times. The review aims to evaluate the biological interactions of Ca, Mg, and selected trace elements with Fe and their roles in certain diseases. Understanding these interactions is crucial for developing strategies to mitigate the adverse effects of these elements on health.