Polyphenolic compounds are widely distributed in the vegetable kingdom and are therefore consumed regularly in the human diet. Epidemiological studies suggest that foods rich in polyphenolic compounds contribute to reducing the risk of cancer. The purpose of our work is to: 1) study the possible cytotoxicity and antiproliferative effects of 13 polyphenolic compounds on 3 cell lines of melanocytes, 2 of melanoma (B16F10 and SK-MEL-1), and 1 of nontransformed melanocytes (Melan-a); and 2) identify the possible relationship between the chemical structure of the tested compounds and their effect on cellular viability. The said polyphenolic compounds corresponded to 8 flavonoids with varying hydroxyl and methoxyl substituents, related structurally through the oxidation state of their flavonoid skeleton, a catechin polymer and 4 phenolic acids. The cytotoxic activity of all the studied compounds was modest or not apparent. The flavonoids luteolin, tangeretin, baicalein, quercetin, and myricetin, and gallic acid showed antiproliferative effects on the tested lines. Our results suggest that a correlation exists between the structural oxidation state and the position, number, and nature of substituents of the polyphenolic compounds studied and their antiproliferative effects.