Objective To compare the efficacy and safety of three regenerative materials in non-surgical facial rejuvenation. Methods A total of 90 patients who underwent non-surgical facial rejuvenation in Xi'an Mylike Medical Beauty Hospital from January 2023 to June 2024 were selected as the research subjects, and they were divided into group A, group B and group C according to different filling materials, with 30 patients in each group. Group A was treated with poly-DL-lactic acid (PDLLA), group B was treated with calcium hydroxyapatite (CaHA), and group C was treated with polycaprolactone (PCL) microspheres. The skin elasticity improvement, skin texture, facial contour lifting effect and complications were compared among the three groups. Results The skin elasticity score of group A after treatment was higher than that of group B and group C (P <0.05). There was no significant difference in skin elasticity score between group B and group C (P >0.05). The skin gloss and smoothness of group A after treatment were better than those of group B and group C (P <0.05). There was no significant difference in gloss and smoothness between group B and group C (P >0.05). There was no significant difference in skin moisture content among the three groups (P >0.05). There were no significant differences in the rate of moderate to severe improvement of facial contour and the incidence of complications among the three groups (P >0.05). Conclusion All three regenerative materials have definite clinical value in facial rejuvenation. PDLLA is good at deep skin elasticity improvement and volume reconstruction, CaHA is superior in immediate filling and bony support, and PCL is suitable for mild blemish modification and sagging lifting. Clinically, individualized selection should be made based on patients' aging characteristics, treatment expectations and material properties.