Objective:　Previous　studies　have　investigated　the　association　between　diabetes　medications　and　thyroid　cancer,　but　the　results　have　not　been　conclusive.　This　study　used　a　Mendelian　randomization　approach　to　investigate　the　causal　relationship　between　diabetes　medications　and　thyroid　cancer　(TC).　Methods:　Exposures　were　six　major　diabetes　medications　target,　while　outcomes　were　TC　and　its　differentiated　forms,　including　papillary　thyroid　carcinoma　(PTC)　and　follicular　thyroid　carcinoma　(FTC).　Mendelian　randomization　was　conducted　using　IVW,　MR-Egger,　and　weighted　median　methods.　Tests　for　heterogeneity,　horizontal　pleiotropy,　and　leave-one-out　were　also　performed.　Results:　In　European　populations,　SGLT2　inhibitors　were　significantly　negatively　associated　with　TC　(OR　0.051,　95%　CI　0.006–0.465,　P　=　0.0082)　as　well　as　PTC　(OR　0.034,　95%　CI　0.003–0.411,　P　=　0.0079),　while　no　correlation　was　found　with　FTC.　These　findings　remained　consistent　even　after　applying　the　Bonferroni　correction.　Conclusions:　The　evidence　suggests　that　SGLT2　inhibitors　could　be　potential　therapeutic　targets　for　TC,　especially　for　PTC,　in　European　populations.　However,　further　large-scale　randomized　controlled　trials　are　necessary　to　verify　their　ability　to　reduce　the　risk　of　and　treat　these　types　of　cancer.　©　Springer-Verlag　Italia　S.r.l.,　part　of　Springer　Nature　2024.