Objective To explore the effect of CO2 laser therapy on skin aesthetics and safety in patients with verruca plana. Methods A total of 100 patients with verruca plana treated in the Department of Dermatology, Nanjing Women and Children's Healthcare Hospital from January 2022 to December 2024 were selected, and they were divided into the control group and the treatment group by the random number table method, with 50 patients in each group. The control group was given 5% imiquimod cream, and the treatment group was given CO2 laser therapy. The clinical efficacy, skin aesthetics, skin recovery time, DLQI score, skin lesion score, adverse reaction rate and recurrence rate were compared between the two groups. Results Compared with the total effective rate of 88.00% in the control group, the total effective rate in the treatment group was higher (96.00%), but the difference was not statistically significant (P >0.05). Compared with the skin aesthetics of 82.00% in the control group, the skin aesthetics in the treatment group was higher (98.00%) (P <0.05). The crusting start time, decrustation start time, and complete decrustation time in the treatment group were shorter than those in the control group (P <0.05). The DLQI and skin lesion scores in the treatment group after treatment were lower than those in the control group (P <0.05). Compared with the control group, the incidence of adverse reactions and recurrence rate in the treatment group were lower (P <0.05). Conclusion CO2 laser therapy demonstrates excellent clinical efficacy in the treatment of verruca plana. It can effectively improve lesion appearance, accelerate wound healing, enhance patients’ quality of life, and has the advantages of high safety and low recurrence rate.