One of the main causes of renal impairment and failure is acute kidney injury (AKI), which has few treatment options that can preserve kidney function. Stem cells represent a promising regenerative tool, among these are stem cells derived from breast milk (Br-dSCs), which have demonstrated greater potential for regenerative capacity and plasticity in several diseases than other types of stem cells (SCs). However, their application in kidney injury disorders still needs to be fully studied, and their underlying regenerative mechanisms still need to be discovered. Thus, the current investigation aimed to examine the Br-dSCs' capacity for regeneration in acute renal injury and address the possible molecular mechanisms implicated in the reparative modalities of these cells regarding cellular autophagy. Eighteen adult male Sprague Dawley rats were assigned into 3 equal groups 10 rats each: control, AKI, and AKI + Br-dSCs groups.  The kidney function tests' serum level, oxidative stress in the kidneys, histopathological examination, immunohistochemical expression of the renal receptor of insulin growth factor 1 (IGF-1r), epidermal growth factor 1 (EGF-1r), autophagy promoting factor beclin-1, and renal collagen deposition were performed. The results illustrated that Br-dSCs improved the serum level of blood urea nitrogen, uric acid, as well as creatinine rendering them to the ordinary physiological tone of the group of control. Moreover, the administration of Br-dSCs markedly increased the IGF-1r, EGF-1r, beclin-1, and downregulated collagen synthesis and deposition. We could conclude that Br-dSCs regenerate the injured kidney tissue via a modulating growth factor receptor that potentially promote the renal autophagy process.