Metabolic syndrome, a cluster status of multiple metabolic disorders, has been one of the most common public health problems in the world. Insulin resistance is acknowledged as an important causative factor in the pathogenesis of metabolic syndrome, which increases the risk of developing hypertension, cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver, and chronic kidney disease. Although some current drugs against metabolic syndrome or its components are available, they are still far from optimal. Novel drugs are urgently needed. Chinese herbal medicine, a promising source for the development of alternative and complementary medicines, shows unique characteristics and vantages in the prevention and treatment of metabolic syndrome. Fructose is a monosaccharide found in fruits, vegetables and honeys. High dietary fructose or extensive commercial use of high-fructose corn syrup (HFSC) can induce insulin resistance and metabolic syndrome, triggering kidney impairment with glomerular podocyte injury and proteinuria. Here, we explored and discussed the biologic mechanism in the pathogenesis of high fructose-induced podocyte injury, in which special attention is paid to oxidative stress, insulin resistance and inflammation. Furthermore, we provided the new experimental evidence regarding the effects of Chinese herbal medicine on fructose-associated podocyte injury in metabolic syndrome.