This study aims to investigate the renal tubular protective effects of salvianolic acid B (Sal B) on cisplatin-induced acute kidney injury (AKI) and its underlying mechanisms. An AKI model in mice was established via intraperitoneal injection of 20 mg/kg cisplatin. Five experimental groups were established: a control group, a model group, a low-dose Sal B (30 mg/kg) treatment group, a high-dose Sal B (60 mg/kg) treatment group, and a positive control group (ferrostatin-1, a ferroptosis inhibitor, 5 mg/kg). Renal function was assessed by measuring blood urea nitrogen and creatinine concentrations. Renal lesions were observed using periodic acid-schiff and hematoxylin and eosin staining. Expression of tubular injury-related proteins kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), along with ferroptosis-related proteins, was detected. The effective concentration of Sal B was determined using the MTT assay. Ferroptosis-related metabolites were detected via Western blot and immunofluorescence staining. Additionally, the SwissTargetPrediction database was used to identify direct targets of Sal B, and its mechanism of action was explored through molecular docking and agonist pretreatment experiments. Results demonstrated that Sal B dose-dependently reduced cisplatin-induced increases in blood urea nitrogen and creatinine, mitigated renal pathological damage, significantly decreased renal expression of injury markers KIM-1 and NGAL proteins, alleviated cisplatin-induced decline in renal glutathione peroxidase 4 (GPX4) protein expression, and reduced Fe²⁺ and malondialdehyde accumulation alongside glutathione depletion. In vitro experiments further demonstrated that Sal B mitigated cisplatin-induced damage in human renal proximal tubular epithelial cells (HK-2) cells by reducing Fe²⁺ and lipid peroxidation accumulation, alleviating intracellular GPX4 protein downregulation, and thereby inhibiting ferroptosis. Screening via the SwissTargetPrediction online database and molecular docking identified matrix metalloproteinase-9 (MMP-9) as a direct target of Sal B. The study also revealed that Sal B decreased cisplatin-induced MMP-9 protein expression; while intervention with an MMP-9 agonist MMP9-IN-1 revealed that increased MMP-9 expression abolished Sal B's regulatory effect on cisplatin-induced ferroptosis in HK-2 cells. In summary, Sal B inhibits cisplatin-induced acute kidney injury and ferroptosis in renal tubular epithelial cells, with MMP-9 serving as a key mediator in Sal B's mitigation of acute kidney injury and suppression of ferroptosis in renal tubular epithelial cells.