In this study, through network pharmacology combined with in vivo animal experiments and in vitro cellular experiments, we demonstrated that YSHS granules modulated the ERS GRP78/CHOP pathway, slowed down the process of hyperglycemia-induced apoptosis, and attenuated the damage of podocytes, which in turn slowed down the progression of DKD (Figure 7). This evidence concerns the gene HSPA5 and diabetic kidney disease.