Objective To explore the differences in clinical efficacy and safety of three different regenerative materials, namely polylactic acid (PLA), polycaprolactone (PCL) and calcium hydroxylapatite (CaHA), in facial rejuvenation treatment. Methods A total of 120 patients who received facial rejuvenation treatment in Wuhan Hanjin Medical Cosmetology Hospital from January 2023 to December 2024 were selected, and they were divided into the PLA group, PCL group and CaHA group according to different application materials, with 40 patients in each group. All groups received local injection of the corresponding materials. The facial firming and volume-increasing effect, adverse reactions and satisfaction were compared among the three groups. Results The skin firmness score of the CaHA group was higher than that of the PLA group and PCL group (P <0.05). The thickness of subcutaneous soft tissue in the PCL group was higher than that in the CaHA group and PLA group (P <0.05). The score of skin elasticity and skin luster in the PLA group was higher than that in the CaHA group and PCL group (P <0.05). The incidence of adverse reactions in the PLA group (2.50%) was lower than that in the PCL group (17.50%) and CaHA group (15.00%) (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the PCL group and CaHA group (P >0.05). There was no statistically significant difference in satisfaction among the three groups (P >0.05). Conclusion PLA, PCL and CaHA have their own advantages in facial rejuvenation treatment. PLA focuses on improving skin texture and color and is the safest, but its volume-increasing effect is weak. Both CaHA and PCL can effectively increase volume. CaHA excels in skin firming, whereas PCL provides a longer-lasting effect. The three materials all have high patient satisfaction.