The residue of chestnut processing generates a large amount of waste material, a resource not adequately exploited. The antioxidant and antitumoral properties of cold and hot water extracts from discarded pericarp of four chestnut Sardinian accessions and one marron variety were studied. The antioxidant capacity of the extracts was determined by spectrophotometric and electrochemical tests. The 1,1-diphenyl-2-pic-rylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) results were highly correlated with each other; likewise, a good correlation was found between Ferric Reducing Antioxidant Power (FRAP) and cyclic voltammetry (CV) values, both based on the direct transfer of electrons. The antiproliferative effect on normal cells (fibroblasts), and on colon (RKO and SW48) and breast (MCF7) cancer cells was evaluated. Additionally, this paper marks the first application of chestnut extracts to investigate their effects on melanoma (B16F10) cells. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test demonstrated that temperature and different extraction times significantly influenced the growth of cells, both normal and tumor. The fibroblast growth was significantly inhibited by moderate doses of cold extracts, while the GI50 values calculated for hot extracts were high, regardless of the accession or cultivar. An even more marked inhibitory action of the cold extracts was observed both on the growth of RKO and SW48 cells and on B16F10 melanoma cells. Otherwise, an extract concentration, both cold and hot, of no less than 243 µg mL−1 is required to achieve a 50% inhibition of MCF7 cell growth.