Objective To explore the application effect of composition of sodium hyaluronate and ectoine in skin barrier repair through different evaluation methods, with a commercially available hyaluronic acid dressing as the control. Methods In vitro skin models were used to determine the effects of 3 samples [skin barrier spray dressing (Sample 1), skin barrier repair dressing (Sample 2) and a commercially available hyaluronic acid dressing (Sample 3)] on improving skin moisture content, inhibiting inflammatory factors and mediators, and promoting the secretion of filaggrin (FLG) and loricrin (LOR). A bilateral human forearm model was applied to the subjects to compare changes in transepidermal water loss (TEWL) after product application. Results The skin moisture content in the sample groups was significantly higher than that in the blank control group (P <0.01). The improvement rates of skin moisture content in Sample 1, Sample 2 and Sample 3 were 73.05%, 74.41% and 84.06% respectively. The contents of IL-1α, TNF-α and PGE2 in the sample groups were lower than those in the negative control group (P <0.05). The contents of IL-1α and PGE2 in Sample 1 and Sample 2 were lower than those in Sample 3 (P <0.05). There was no significant difference in TNF-α content among Sample 1, Sample 2 and Sample 3 (P >0.05). The inhibition rates of IL-1α in Sample 1, Sample 2 and Sample 3 were 25.11%, 43.40% and 10.64% respectively. The inhibition rates of TNF-α in Sample 1, Sample 2 and Sample 3 were 28.25%, 25.22%, and 33.41% respectively. The inhibition rates of PGE2 in Sample 1, Sample 2 and Sample 3 were 37.21%, 32.12%, and 18.28% respectively. The contents of FLG and LOR in the sample groups were significantly higher than those in the negative control group (P <0.01). The contents of FLG and LOR in Sample 2 were significantly higher than those in Sample 3 (P <0.01). The improvement rates of FLG in Sample 1, Sample 2 and Sample 3 were 92.31%, 169.23% and 76.92% respectively, and the improvement rates of LOR were 326.32%, 384.21%, and 52.63% respectively. Sample 1 inhibited TEWL at 1, 2, and 4 hours after application (P <0.05). Sample 2 inhibited TEWL at 2 hours after application (P <0.05). Conclusion The composition of sodium hyaluronate and ectoine shows a significant synergistic effect in skin barrier repair. It can synergistically inhibit the release of IL-1α inflammatory factor and PGE2 inflammatory mediator, promote the secretion of FLG and LOR, and improve skin barrier function in terms of moisturizing, soothing and repairing, providing a new idea for the intervention and repair of skin barrier damage.