Cis-Diamminedichloroplatinum (II) (DDP)-induced nephrotoxicity (DDPIN) may cause irreversible renal injury associated with high morbidity and mortality. Current standard therapies have not achieved satisfactory clinical outcomes due to unclear molecular and cellular mechanisms. Therefore, exploring potential therapies on DDPIN represents an urgent medical need. Present study characterized the role of lncRNA maternally expressed gene 3 () in the pathogenesis of DDPIN. In both and in murine models of DDP-induced nephrotoxicity, exacerbated DDPIN by negatively regulating miRNA-126 subsequently causing a decreased AKT/TSC/mTOR-mediated autophagy. By silencing or incorporating miRNA-126 mimetics, the proliferation and migration of DDP-treated cells were restored. , we identified Paeonol to alleviate DDPIN by the inhibition of . Taken together, represents a novel therapeutic target for DDPIN and Paeonol may serve as a promising treatment by inhibiting and its related signaling pathways.