Objective To determine if saikosaponin D (SSD) alleviates renal injury and fibrosis in chronic kidney disease ( CKD) models by regulating the long non-coding RNA-gm33782 ( LncRNA-gm33782), thereby modulating the glycolysis pathway. Methods A CKD model was established in C57BL / 6 mice using unilateral ureteral obstruction (UUO). Thirty mice were assigned randomly to sham group, UUO group, SSD-L group(30 mg / kg), SSD-H group (60 mg / kg), and Irb group(20 mg / kg) (n = 6 mice per group). After oral administration for 7 d, the mice were euthanized and kidneys harvested. Renal pathological injury was assessed using hematoxylin-eosin (HE), Masson, and Sirius red staining. Fibrosis markers ( fibronectin ( FN), α-smooth muscle actin( α-SMA),collagen 1 (Col-Ⅰ)) were detected by immunohistochemistry and Western Blot. LncRNA-gm33782 expression was quantified by RT-qPCR. Renal lactate concentration was measured and hexokinase 2 (HK2) protein expression was assessed by Western Blot to evaluate associations between LncRNA-gm33782 and renal fibrosis and glycolysis. An in vitro fibrosis model was induced in mouse renal tubular epithelial cells ( TCMK-1) by transforming growth factor (TGF)-β induction. Knockdown and overexpression of LncRNA-gm33782 were employed to assess its effects on fibrosis markers ( FN, Col-Ⅰ), glycolysis-associated proteins ( HK2, pyruvate kinase M2), and mitochondrial function ( cellular oxygen consumption rate, OCR ). SSD intervention was applied under LncRNA-gm33782- overexpression conditions to evaluate its protective effects. Results SSD significantly attenuated renal tissue injury,fibrosis, and lactate accumulation in UUO mice. LncRNA-gm33782 was significantly upregulated in in vivo (UUO) and in vitro fibrosis models ( P<0. 05 ). SSD reduced LncRNA-gm33782 expression ( P<0. 05 ). In vitro knockdown of LncRNA-gm33782 ameliorated TGF-β-induced cellular fibrosis and suppressed glycolytic activation,while its overexpression exacerbated mitochondrial OCR suppression, fibrosis, and glycolytic activation, and attenuated the protective effects of SSD ( P<0. 05). Conclusions SSD alleviates renal fibrosis primarily by targeting and suppressing LncRNA-gm33782 expression, leading to downregulation of glycolytic activation and restoration of mitochondrial function. LncRNA-gm33782 is a key molecular target mediating the renoprotective effects of SSD.