Although oral antidiabetic agents are widely prescribed for management of type 2 diabetes mellitus (T2DM), their long-term mutagenic and carcinogenic safety remains insufficiently characterized. The aim of this study was to examine the genotoxic potential of empagliflozin, linagliptin, pioglitazone, and the fixed-dose combination (empagliflozin/linagliptin) using Somatic Mutation and Recombination Test (SMART) in . Third-instar larvae from standard (ST) and high-bioactivation (HB) crosses, differing in cytochrome P450 enzyme activity, were chronically exposed to increasing concentrations of selected drugs. Empagliflozin, linagliptin, and their combination did not induce significant alterations in mutant clone frequency across all tested doses in either cross. In contrast, the highest concentration of pioglitazone (72 mg/ml) significantly elevated DNA damage, with lesions originating from both mutation and recombination in the ST cross, but almost exclusively from mutational events in the HB cross. These findings suggest that while empagliflozin and linagliptin present no apparent detectable genotoxic hazard under these tested conditions, pioglitazone displays a dose-dependent genotoxic effect. Data indicate the importance of systematic genotoxicity assessment in widely used antidiabetic medications to ensure patient safety.