Oxidative stress induced by hyperglycemia is thought to play an important role in the pathogenesis of diabetic nephropathy (DN). NRK-52E mouse renal epithelial cells (NRK-52E) retained the properties of normal proximal renal tubule cells, when NRK-52E cells were cultured in glucose-enriched medium, renal cells were Apoptotic death causes high oxidative stress. Treatment of hyperglycemic (HG) proximal tubule damage has emerged as a potential treatment option to reduce the onset and progression of DN. The present study aimed to investigate the regenerative effects of Phyllanthus emblica and Tinospora cordifolia on HG-induced cytotoxicity in NRK-52E cells. Aqueous extracts of Phyllanthus emblica and Tinospora cordifolia were prepared using a rotary vacuum evaporator. Cell viability was assessed using the MTT assay kit (Hi-media) and the flow cytometric assay kit (Sigma) used to detect apoptosis. Treatment of cells with HG significantly reduced cell viability while significantly increasing reactive oxygen species (ROS) content. In this study, we hypothesized that the excessive induction of ROS by increased glucose plays a key role in the apoptosis of NRK-52E cells. Cell treatment with Phyllanthus emblica and Tinospora cordifolia ameliorated these HG-induced changes. Thus, Phyllanthus emblica, Tinospora cordifolia and their combination exhibited cytoprotective effects against HG culture-induced renal cell damage by inhibiting oxidative stress and mitochondrial apoptosis.