Overall, the administration of salidroside not only demonstrates an externally marked hypoglycemic and hypolipidemic effect but also intrinsically ameliorates DN by activating the AMPK/SIRT1, Nrf2/HO-1, Akt/ILK, Sirt1/PGC-1α, and Akt/GSK-3β, AMPK/Cav-1 pathways while suppressing the TXNIP-NLRP3, ERK1/2, and TGF-β1/Smad, ROS/Src/Cav-1 pathways to suppress cellular apoptosis, oxidative stress, and inflammation. Here, PPARGC1A is linked to liver dysplastic nodule.