Objective To analyze the effect of 3D printing digital guide in repairing mandible defect and functional reconstruction with fibular musculocutaneous flap. Methods Fifty patients who received fibula musculocutaneous flap for mandibular defect repair and functional reconstruction in our hospital from January 2020 to March 2022 were selected as observation objects. According to different treatment methods, they were divided into control group (traditional surgical treatment) and observation group (3D printing digital guide technology assisted with fibula musculocutaneous flap repair surgery), with 25 patients in each group. Surgical indicators, hospitalization and postoperative recovery, repair accuracy, repair satisfaction and quality of life (UW-QOLscores) were compared. Results The operation time and hospital stay of the observation group were shorter than that of the control group, the intraoperative blood loss was less than that of the control group, and the mouth opening score of the observation group was higher than that of the control group at 3 months after the operation (P<0.05). The mean displacement of condyle, mandibular angle and chin were lower than those in control group (P<0.05). The scores of aesthetic satisfaction, mastication satisfaction, articulation satisfaction and occlusal relationship satisfaction were higher than those of control group (P<0.05). The score of UW-QOL was higher than that of control group (P<0.05). Conclusion The application of 3D printing digital guide technology provides good technical support for the repair operation of fibular musculocutaneous flap, which can play an ideal therapeutic effect for mandibular defects and functional reconstruction after resection of various benign tumors in the mandible, optimize the surgical indicators, improve the accuracy of mandible repair, restore facial appearance, improve the mastics and articulation functions, and improve the quality of life of patients, with good clinical application value.