Provided are peptides that bind to the thymidylate synthase protein, in particular to human thymidylate synthase (hTS) protein, for the treatment of cancer. Further provided are peptides that can bind at a binding site located at the interface of thymidylate synthase protein. These peptides range from 3 to 10, preferably 4-8 amino acids and have a sequence that binds to each subunit of the thymidylate synthase dimer at the level of dimer interface, stabilizing the dimeric inactive form of the thymidylate synthase enzyme. In addition, provided are pharmaceutical compositions including these compounds as active agents, and uses thereof for the treatment of cancer and to reverse or/and be active in cancer drug resistance.