This research aims to investigate the nephro-protective effects of alogliptin and the supportive effects of L-carnitine in nephrotoxicity produced by gentamicin in male Wistar rats when coupled with a dipeptidyl pepetidase-4 (DDP-4) inhibitor. Five equal groups (G) of 25 male albino rats, each weighing 130 ± 5.7 g, were created: G1 (control negative), G2 (control positive, nephrotoxic), G3 (L-carnitine-treated group), G4 (Alogliptin-treated group),and G5 (treated with alogliptin and L-carnitine). Significant variations were found in the biochemical analyses of the serum total protein, albumin, urea, uric acid, and creatinine. (P˂0.05) among groups, and the mean value of these parameters revealed that G5 was significantly different from G3 and G4. The concentration of malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT), and super oxide dismutase (SOD) were measured in order to determine the oxidative/antioxidant cascades. The mean value of these parameters revealed significant differences (P< 0.05) between various groups, with G5 being significantly different from G3 and G4. In gentamicin-induced nephrotoxicity models in rats, the findings of the histological and histochemical analyses suggest that alogliptin and L-carnitine may have a role in preventing the destruction of renal tissue. L-carnitine or alogliptin therapyappeared to preserve the kidney by its antioxidant effect as evidenced by the enhancement of biochemical indices, oxidant state, as well as the recovery of the kidney structural stability and its function.When the two medications are used together, the results are better than using each one separately. The improvement of physiological markers and antioxidant state, as well as the restoration of the kidney's structural integrity and function, demonstrate how administration of alogliptin or L-carnitine maintains the renal through their antioxidant effects. The results are better when the two drugs are taken together rather than individually.