Objective To analyze the effect of fractional laser combined with polydeoxyribonucleotide (PDRN) on the overall aesthetic improvement in patients undergoing facial skin rejuvenation. Methods A total of 90 patients who received facial skin rejuvenation treatment in our hospital from January 2022 to June 2023 were selected, and they were divided into the control group and the observation group by the random number table method, with 45 patients in each group. The control group received single fractional laser treatment, and the observation group received fractional laser combined with PDRN treatment. The skin gloss porphyrin index, skin texture, pore improvement, overall aesthetic improvement, satisfaction and adverse reactions were compared between the two groups. Results After 1, 3 and 6 months of treatment, the scores of skin gloss porphyrin index, skin texture and pore improvement in the two groups were higher than those before treatment, and those in the observation group were higher than those in the control group (P<0.05). The total effective rate of treatment in the observation group (88.89%) was higher than that in the control group (66.67%) (P<0.05). The satisfaction rate of the observation group (91.11%) was higher than that of the control group (66.67%) (P<0.05). There was no statistically signiffcant difference in the incidence of erythema and edema between the two groups (P>0.05). The duration of erythema and edema in the observation group was shorter than that in the control group (P<0.05). Conclusion Compared with single fractional laser treatment, fractional laser combined with PDRN treatment can synergistically improve facial skin gloss, delicacy and enlarged pores, achieve ideal overall aesthetic improvement effect, effectively improve patient satisfaction, and does not increase the risk of adverse reactions.