Objective To investigate the protective effect of Dendrobium officinale polysaccharides (DOP) against aluminum (Al)-induced hepatocyte ferroptosis and its underlying mechanisms. Methods LO2 cells were treated with increasing concentrations of aluminum chloride (AiCl3) to determine its half-maximal inhibitory concentration (IC50). The impact of DOP on AiCl3-induced LO2 cell viability and proliferation was analyzed using CCK-8 assay. Hepatocyte apoptosis was examined by flow cytometry. Protein expression of hepatic fibrosis markers (α-SMA and COL1α1) and iron death markers (GPX4 and xCT) was assessed using Western blot technique. Intracellular ROS levels were detected using DCFH-DA fluorescent probe. Results Treatment with AiCl3 resulted in a significant decrease in LO2 cell viability and proliferation, accompanied by a significant increase in cell apoptosis rate. The expression of α-SMA and COL1α1 proteins was significantly upregulated (P<0.001). Additionally, AiCl3 treatment markedly elevated ROS levels and downregulated the expression of GPX4 and xCT proteins. These changes were significantly reversed upon addition of DOP treatment. Conclusion Dendrobium officinale polysaccharides effectively reversed LO2 cell apoptosis and the decline in cell viability induced by aluminum exposure by inhibiting oxidative stress and modulating the expression of GPX4 and xCT proteins. This demonstrates a protective role against hepatocellular ferroptosis and liver damage, offering new therapeutic targets for the prevention and treatment of liver diseases associated with aluminum exposure