The invention relates to tetrahydroberberine thiadione compounds as well as a preparation method and an application thereof and belongs to the technical field of chemical synthesis. The tetrahydroberberine thiadione compounds are shown in a general formula I-X, have certain inhibition activity for growth of gram-positive bacteria, gram-negative bacteria and fungi, can be used for preparing drugs for resisting bacteria and/or fungi, have no obvious drug resistance, can be combined with norfloxacin and fluconazole to more efficiently inhibit growth of bacteria and fungi and can also be intercalated into DNA to be used as a DNA intercalating agent. Besides, the preparation materials are simple, cheap and easy to obtain, the synthesis route is short and the compounds have great significance inapplication in infection resistance.