The HZI headquarter is located in Braunschweig where it was founded in 1965. Since 2009 the HZI has a branch in Saarbrücken: the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) with its research on natural products, their chemical optimisation and investigation of biological barriers.

At the Hamburg location, the HZI researchers work on the campus of the German Electron Synchrotron (DESY). Together with other scientific partners, HZI and DESY established the Centre for Structural Systems Biology (CSSB) in 2011.