Objective To explore the application value of transdermal delivery of recombinant type Ⅲ collagen combined with micro-focused ultrasound in the treatment of sensitive skin. Methods A total of 68 patients with sensitive skin in Chengdu Gaoxin Xuzhang Medical Cosmetology Clinic from January 2023 to June 2024 were selected and divided into the control group and the experimental group according to the random number table method, with 34 patients in each group. The control group received micro-focused ultrasound treatment, and the experimental group received transdermal delivery of recombinant type Ⅲ collagen combined with micro-focused ultrasound treatment. The clinical efficacy, adverse reactions, and red area scores, nasolabial fold scores and marionette line scores at different time points [before treatment (T0), immediately after the first treatment (T1), 1 week after the first treatment (T2), 1 month after the first treatment (T3), 1 month after the second treatment (T4), 1 month after the third treatment (T5), 6 months after the end of treatment (T6)] were compared between the two groups. Results The total effective rate of the experimental group was 94.12%, which was higher than 76.47% of the control group (P <0.05). The incidence of adverse reactions in the experimental group was 2.94%, which was lower than 11.76% in the control group (P <0.05). The red area scores in the experimental group at T1-T6 were lower than those in the control group (P <0.05). The nasolabial fold scores in the experimental group at T3-T6 were lower than those in the control group (P <0.05). The marionette line scores in the experimental group at T2-T6 were lower than those in the control group (P <0.05). Conclusion The combination of non-invasive iontophoretic transdermal drug delivery system for recombinant type Ⅲ collagen and micro-focused ultrasound in the treatment of sensitive skin has a definite effect, which can improve the aging manifestations such as facial red area, nasolabial fold, and marionette lines, with high safety.