Objective To explore the effect of two-dimensional intensive nursing on aesthetic effect of vitiligo patients treated by fractional CO2 laser combined with pimecrolimus cream. Methods A total of 60 vitiligo patients treated by fractional CO2 laser combined with pimecrolimus cream in the Fifth Affiliated Hospital of Southern Medical University from January 2022 to June 2024 were selected as the research subjects, and they were divided into control group (n =30) and experimental group (n =30) by the random number table method. The control group was given conventional nursing, and the experimental group was given two-dimensional intensive nursing on the basis of the control group. The intervention effect, negative emotions, aesthetic effect satisfaction, quality of life and nursing satisfaction were compared between the two groups. Results The total effective rate in the experimental group was 93.33%, which was higher than 70.00% in the control group (P <0.05). After 4 weeks of intervention, the scores of SAS and SDS in the experimental group were lower than those in the control group (P <0.05). The aesthetic effect satisfaction rate in the experimental group was 93.33%, which was higher than 70.00% in the control group (P <0.05). After 4 weeks of intervention, the score of DLQI in the experimental group was lower than that in the control group (P <0.05). The nursing satisfaction in the experimental group was 93.33%, which was higher than 73.33% in the control group (P <0.05). Conclusion The application of two-dimensional intensive nursing on vitiligo patients treated by fractional CO2 laser combined with pimecrolimus cream can effectively improve their negative emotions and quality of life, and patient’s aesthetic effect satisfaction and nursing satisfaction are high, which is worthy of clinical application.