Background Diabetes mellitus (DM) affects more than 30 million people in the United States. About one-third of DM patients develop diabetic kidney disease (DKD). Metformin is a widely prescribed antidiabetic medication for patients with type 2 diabetes; however, its direct effects on renal function are poorly understood. Hence, our study aimed to investigate the effects of a non-glucose lowering, low-dose metformin treatment against the progression of DKD using a genetic mouse model of type 2 diabetes. Methods Our study utilized db/db mice, which spontaneously develop type 2 diabetes due to a mutation in leptin receptors. To aggravate the degree of renal injury, each mouse had its left kidney removed at ten weeks of age. Heterozygous, non-diabetic mice were used as the control group. The study had four treatment groups: 1) vehicle-treated control, 2) metformin-treated control, 3) diabetic, vehicle-treated, and 4) diabetic, metformin-treated. Mice were treated with either vehicle or metformin (100 mg/kg/day) for four weeks. Urine and kidney tissue samples were collected at the end of the study to measure the markers of renal dysfunction, such as elevations in urine albumin-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1), and the markers of renal fibrosis, such as transforming growth factor-beta (TGF-β) and alpha-smooth muscle actin (α-SMA). Results Our results indicate that low-dose metformin-treatment decreased UACR (117.53 ± 61.56 vs. 205.3 ± 112.5); however, it did not alter the elevated fasting blood glucose levels or plasma creatinine levels in diabetic mice. Kidneys from metformin-treated diabetic mice revealed reduced KIM-1 immunostaining (1.5 ± 0.5 vs. 2.3 ± 0.7) compared to vehicle-treated diabetic mice. Similarly, the metformin-treated diabetic mice kidneys showed decreased immunostaining for TGF-β (0.7 ± 0.2 vs. 1.3 ± 0.3). Moreover, the renal protein expression of α-SMA (assessed via western blotting) was significantly reduced in metformin-treated diabetic mice than the vehicle-treated counterparts. Conclusion Our findings suggest that low-dose metformin treatment ameliorates renal dysfunction and fibrosis associated with DKD. Future studies are warranted to ascertain the renoprotective effects of low-dose Metformin treatment against the progression of DKD.