The present invention provides a novel SIRT6 small molecule agonist and applications thereof, wherein the agonist is a tricyclic bisulfamide derivative represented by a formula (1) or a formula (2) ora pharmacologically acceptable salt thereof, in the formula (1), R1 and R2 are the same or different, and represent methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl(2-methylbutane) and hexyl, in the formula (2), R3 represents a nitrogen-containing tertiary amine aliphatic ring and a derivative thereof containing a substituent, and the nitrogen-containing tertiaryamine aliphatic ring comprises azacyclopropane, azacyclobutane, a pyrazole ring, a morpholine ring, a piperidine ring, a piperazine ring, azecycloheptane and azacyclooctane. According to the present invention, the efficient low-toxic SIRT6 small molecule agonist is designed and synthesized, can obviously activate the activity of SIRT6 in in-vitro experiments, is subjected to related research and activity evaluation on colon cancer cell lines in vivo, and has important significance in the development of drugs for diseases.