Poly-L-histidine hydrochloride is widely used in biotechnology and biomedical research due to its ability to bind metal ions, particularly nickel, cobalt, and copper. This property makes it valuable in protein purification processes, where it is often employed as a tag in immobilized metal affinity chromatography (IMAC) to isolate and purify recombinant proteins. Additionally, it is utilized in the development of drug delivery systems, where its histidine residues facilitate endosomal escape, enhancing the efficiency of intracellular delivery of therapeutic agents. Its buffering capacity in acidic environments also makes it suitable for use in pH-sensitive applications, such as in the design of smart biomaterials and controlled-release systems. Furthermore, it is explored in tissue engineering for its potential to improve cell adhesion and proliferation on scaffold surfaces.