Palladium (Pd) is a metal frequently used for dental alloys. In order to elucidate controversial options about Pd concerning its biological performances, our study consists in the evaluation of commercial and experimental PFM and C&B precious and semi-precious dental alloys. This investigation was also designated to the establishment of a cytotoxicity index (CI) such as it was described for hemocompatibility testing. The following materials were tested: 36 commercial alloys (Au-, Pd- and Ag-base), 14 experimental alloys (Pd-base established by an experience plan) and pure metals (Ag, Au, Cu, Ni, Cr, In, Sn, Pt, Ti, Zn). The cells culture experiments were carried out with epithelial L132 cells and NIH 3T3 fibroblasts. In vitro cell viability tests show that Pt, Sn, In, Ti, Au and Pd have no cytotoxic effect; Cr, Cu and Ag are toxic, Ni, Zn, and Co are highly toxic. An identical ranking was found with the inflammatory and proliferation tests. Toxic and highly toxic metals induced slight or strong prosthetic dental restoration morphological alterations after 3-days cultures and mostly cell death after 6-days cultures. These effects are dependent on the leakage of the element into the culture medium as revealed by ICP. The addition of Au gives benefit to Pd–Ag alloys, but does not produce any major effect on Pd–Cu alloys. This qualitative ranking can quantitatively be confirmed by cytocompatibility testing after application of a CI.