Retinoids are one of the most effective drugs in inducing complete or prolonged remission of severe acne vulgaris, but the adverse reactions associated with the use of them are raising a concern about the potential effect of these drugs on internal organs function such as the kidney. The aim of this review is to comprehensively gather data about isotretinoin, both potential adverse and beneficial effects on the kidney based on the current experimental and clinical findings. Very few studies, including five case reports, described that systemic oral isotretinoin within usual doses (40 mg/day or 0.5 mg/kg⁄day) within 1 to 4 months of treatment might be associated with different types of renal dysfunctions. These include acute interstitial nephritis, nephrotic syndrome, and hematuria with dysuria. The adverse reactions of systemic isotretinoin on the kidney and urinary system are unlikely and rare. In contrast, six experimental studies demonstrated the beneficial effects of either oral or parenteral low- (2 or 5 mg/kg/day) or high- (10, 20, 25, 40 mg/kg/day) dose isotretinoin on the kidney in the rat models of glomerulonephritis, obstructive nephropathy or allograft nephropathy. The nephroprotective functions of isotretinoin in these studies were attributed to its anti-proliferative, anti-fibrotic, and anti-inflammatory actions. However, clinical studies are warranted to elucidate the possible beneficial effects of isotretinoin in preventing or attenuating kidney injury in different settings.