Over the past few decades, diabetes mellitus, including types 1 and 2, has imposed huge burdens on public health, including high mortality and treatment difficulty (Bellary, Kyrou, Brown, & Bailey, 2021; Schmidt, 2018). Unfortunately, many attempts to treat and prevent diabetes have failed due to the dynamic progress of its complications. Among them, diabetic nephropathy (DN), also called diabetic kidney disease (DKD), is the most common complication of diabetes. Statistically, at least 30% of diabetic patients are affected by DN, causing huge burdens on public health (Samsu, 2021). Extensive clinical evidence has revealed that DN is a major cause of end-stage renal disease and a major risk factor for cardiovascular disease (Cohen et al., 2010). The latest report shows that DN contributed to one-third of the disability-adjusted life-years of all chronic kidney disease patients worldwide from 1997 to 2017 (Collaboration, 2020). Studies have shown that the prevalence of chronic kidney disease in China has reached 10.8% (Zhang et al., 2012), the incidence is increasing each year, and this has become a serious public health problem. Although multiple therapeutic methods, including drugs, dietary interventions and other complementary interventions, have been developed to alleviate the development of DN and kidney damage, the ultimate therapeutic effect is unsatisfactory.

Natural products mainly derived from herbs, have been explored as drug sources for a long history to treat a variety of major diseases. To date, lots of passionate endeavors have been made to support and validate the potential effects of experimental study and clinical application of natural products(Newman & Cragg, 2020). Recently, an enormous number of natural products have been reported to alleviate DN induced renal disorders by regulating various biological signalling pathways in preclinical studies (Hu et al., 2021; Yaribeygi, Simental-Mendía, Butler, & Sahebkar, 2019). Some natural products further display beneficial efficacy to treat DN in clinical trials, which validates promising therapeutic strategies. Here, the current review discusses some important biological mechanisms relevant to DN and the potential of representative natural products for the treatment of DN over years via the representative signalling pathways.