Diabetic nephropathy (DN) is a leading cause of end-stage renal failure， and no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from ， and our previous studies showed the cardioprotective and neuroprotective effects of NGR1. However， its role in protecting against DN remains unexplored. Herein， we established an experimental model in / mice and HK-2 cells exposed to advanced glycation end products (AGEs). The in vivo investigation showed that NGR1 treatment increased serum lipid， β2-microglobulin， serum creatinine， and blood urea nitrogen levels of / mice. NGR1 attenuated histological abnormalities of kidney， as evidenced by reducing the glomerular volume and fibrosis in diabetic kidneys. In vitro， NGR1 treatment was further found to decrease AGE-induced mitochondria injury， limit an increase in reactive oxygen species (ROS)， and reduce apoptosis in HK-2 cells. Mechanistically， NGR1 promoted nucleus nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions to eliminate ROS that induced apoptosis and transforming growth factor beta (TGF-β) signaling. In summary， these observations demonstrate that NGR1 exerts renoprotective effects against DN through the inhibition of apoptosis and renal fibrosis caused by oxidative stress. NGR1 might be a potential therapeutic medicine for the treatment of DN.