Minerals play an important role in maintaining human health as the deficiency of these minerals can lead to serious health issues. To address these deficiencies, current research efforts are actively investigating the utilization of protein-mineral complexes as eco-friendly, non-hazardous, suitable mineral fortifiers, characterized by minimal toxicity, for incorporation into food products. Thus, we reviewed the current challenges in incorporating the cereal-legume protein-inorganic minerals complexes’ structure, binding properties, and toxicity during fortification on human health. Moreover, we further reviewed the development of protein-mineral complexes, characterization, and their food applications. The use of inorganic minerals has been associated with several toxic effects, leading to tissue-level toxicity. Cereal- and legume-based protein-mineral complexes effectively reduced the toxicity, improved bone mineral density, and has antioxidant properties. The characterization techniques provided a better understanding of the binding efficiency of cereal- and legume-based protein-mineral complexes. Overall, understanding the mechanism and binding efficiency underlying protein-mineral complex formation provided a novel insight into the design of therapeutic strategies for mineral-related diseases with minimal toxicity.