The study was conducted to characterize mineralogical and elemental composition of mine tailings in order to evaluate the environmental hazards, and identify the metal accumulation potential of native plant species from São Domingos mine, one of the long-term activity mines of the Iberian Pyrite Belt dating back to pre-Roman times. The mine tailings including soils and different plant species from São Domingos were analyzed for determination of tailings characteristics and chemical element contents in tailings and plants. The large amounts of mining wastes are causing significant adverse environment impacts due to acid mine drainage production and mobilization of potentially toxic metals and metalloids in residential areas, agricultural fields, downstreams, and rivers. The typical mineralogical composition is as follows: quartz, micas, K-feldspar, olivine-group minerals, magnetite, goethite, hematite, jarosite, and sulfides. The mine tailings were highly contaminated by As, Ag, Cr, Hg, Sn, Sb, Fe, and Zn; and among them, As and Sb, main contaminants, attained the highest concentrations except Fe. Arsenic has exhibited very good correlations with Au, Fe, Sb, Se, and W; and Sb with As, Au, Fe, Se, Sn, and W in tailings. Among the all plant species, the higher concentrations of all the metals were noted in Erica andevalensis, Erica australis, Echium plantagium, and Lavandula luisierra. Considering the tolerant behavior and abundant growth, the plant species Erica australis, Erica andevalensis, Lavandula luisierra, Daphne gnidium, Rumex induratus, Ulex eriocladus, Juncus, and Genista hirsutus are of major importance for the rehabilitation and recovery of degraded São Domingos mining area.