Objective To investigate the protective effect of Haematococcus pluvialis (H. pluvialis) powder on lipopolysaccharide (LPS)-induced oral epithelial damage.Methods The effects of different doses of H. pluvialis on the viability of human oral keratinocytes (HOKs) were assessed. In LPS-induced HOKs, changes in the tight junction-associated proteins ZO-1 and Occludin, mitochondrial morphology, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial superoxide (MitoSOX), and mitochondrial permeability transition pore (MPTP) were evaluated.Results Compared with the LPS model group, high-dose H. pluvialis significantly upregulated the expression levels of Occludin and ZO-1 to 151.56% and 170.52%, respectively (P < 0.05), and promoted their membrane localization. In addition, H. pluvialis markedly improved LPS-induced excessive ROS and MitoSOX production, the reduction in MMP, and the increase in MPTP in HOKs.Conclusion H. pluvialis may alleviate LPS-induced barrier damage in HOKs by improving mitochondrial dysfunction and reducing oxidative stress, suggesting its potential as a functional food for oral mucosal barrier repair.