A novel strategy was developed for the mitigation of arsenic and mercury surface contaminants found on Haudenosaunee medicine masks. This strategy combined the replacement of specific components of the masks, the application of a surface active displacement solution (SADS), and the use of traditional cleaning methods. Initial efforts focused on the mitigation of medicine masks deemed highly contaminated with mercury; the results indicated more than 99% reduction in dislodgeable residues. The focus of this study was on the mitigation of arsenic residues after a single application of the SADS formulation as well as the removal and replacement of certain components of the masks. The results demonstrated that only trace amounts of arsenic remained and that the overall contaminant reduction was comparable with that previously obtained for mercury.