Abstract Dent's disease is a rare inherited renal disorder characterized by generalized proximal tubule dysfunction with low molecular weight proteinuria, hypercalciuria, and urinary loss of other solutes. The disease is progressive and leads to chronic kidney disease. To study the mechanisms involved in its progression, we generated a knock‐in mouse model displaying a classical Dent's disease type 1 phenotype. Currently, no targeted therapy exists for Dent's disease; treatment strategies primarily aim to slow the progression of specific clinical aspects. Accordingly, empagliflozin [a sodium–glucose cotransporter 2 (SGLT2) inhibitor] known to exert nephroprotective effects and to slow down the decrease of the glomerular filtration rate in diabetic and non‐diabetic patients with chronic kidney disease, was administered to the knock‐in mice. We demonstrated that empagliflozin administration reduces renal and urinary levels of the marker of tubular damage, Lipocalin‐2 (LCN2). However, we observed that this preventive treatment does not alleviate low molecular weight proteinuria, hypercalciuria, inflammation, renal fibrosis or the decline of the glomerular filtration rate. Overall, our findings suggest that SGLT2 inhibition with empagliflozin does not prevent the progression of Dent's disease type 1 towards chronic kidney disease.