Objective To explore the application of Biofunctional Prosthetic System (BPS) in complete denture restoration and its influence on patients’ comfort and masticatory efficiency. Methods A total of 100 patients with complete edentulism admitted to Guangxi Zhuang Autonomous Region Nationalities Hospital from July 2023 to July 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 50 patients in each group. The control group was given conventional complete denture restoration, and the observation group was given BPS. The number of soft-tissue pressure points caused by dentures, comfort, masticatory efficiency and quality of life were compared between the two groups. Results At 1 month after restoration, the number of soft-tissue pressure points caused by dentures in the observation group was (1.32±0.84), which was less than (3.04±1.26) in the control group (P <0.05). At 6 months after restoration, the comfort score and absorbance value of masticatory efficiency in the observation group were higher than those in the control group (P <0.05). The scores of physical, psychological, social relationship and environmental domains in the observation group at 6 months after restoration were higher than those in the control group (P <0.05). Conclusion Compared with traditional restoration methods, the application of BPS for complete denture restoration can more effectively reduce soft-tissue tenderness after denture wearing, improve masticatory efficiency and long-term wearing comfort, as well as enhance patients’ quality of life across multiple dimensions, including physiological, psychological, social, and environmental domains.