Objective To analyze the effect of point-to-point whole-course nursing combined with physical and mental nursing on quality of life and psychological status in patients with moderate to severe acne. Methods A total of 60 patients with moderate to severe acne who were treated in our hospital from August 2023 to August 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group received conventional nursing, and the observation group received point-to-point whole-course nursing combined with physical and mental nursing on the basis of the control group. The quality of life, psychological status and skin barrier function were compared between the two groups. Results After nursing, the total DLQI score of the observation group was lower than that of the control group (P<0.05). After nursing, the scores of SAS and SDS in the observation group were lower than those in the control group (P<0.05). After nursing, the TEWL and sebum secretion rate in the observation group were lower than those in the control group, while the stratum corneum hydration was higher than that in the control group (P <0.05). Conclusion For patients with moderate to severe acne, the application of point-to-point whole-course nursing combined with physical and mental nursing can effectively improve patients’ psychological status, relieve anxiety and depression, enhance quality of life, and optimize skin barrier function, which is worthy of clinical nursing application.