Anthropogenic sources of xenobiotic metals with no physiological benefit are increasingly prevalent in the environment. The platinum group metals (Pd, Pt, Rh, Ru, Os, and Ir) are found in marine and plant species near urban sources, and are known to bioaccumulate, introducing these metals into the human food chain. Many of these metals are also being used in innovative cancer therapy, which leads to a direct source of exposure for humans. This paper aims to further our understanding of nontraditional metal metabolism via metallothionein, a protein involved in physiologically important metal homeostasis. The aggressive reaction of metallothionein and dirhodium(II) tetraacetate, a common synthetic catalyst known for its cytotoxicity, was studied in detail in vitro. Optical spectroscopic and equilibrium and time-dependent mass spectral data were used to define binding constants for this robust reaction, and molecular dynamics calculations were conducted to explain the observed results.