To investigate the effect of recombinant mussel adhesive proteins on pruritus, erythema and skin barrier function in patients with sensitive skin, and to evaluate its efficacy and safety. Methods A total of 70 patients with mild to moderate sensitive skin admitted to our hospital from July 2021 to July 2022 were selected as the research objects. They were divided into study group and control group by random number table method, with 35 patients in each group. The study group was given recombinant mussel adhesive proteins gel, and the control group was given the product gel matrix. The pruritus, erythema value, skin physiological parameters, clinical efficacy and adverse reactions were compared between the two groups before and after treatment. Results At 7 and 28 days after treatment, the VAS score and erythema value of the study group were lower than those of the control group (P <0.05). At 7 and 28 days after treatment, the percutaneous water loss and keratinized mantle in the study group were lower than those in the control group, and the sebum content and stratum corneum hydration were higher than those in the control group (P <0.05). The total effective rate of treatment in the study group was 88.57%, which was higher than 65.71% in the control g roup (P <0.05). No serious adverse reactions occurred in the two groups during the treatment. Conclusion Recombinant mussel adhesive proteins is safe and effective in the treatment of mild and moderate sensitive skin. It can effectively improve the damaged skin barrier and relieve skin itching and erythema, which is worthy of clinical application.