This study aimed to use reconstructive methods for complex oral and maxillofacial defects, explore their feasibility, and evaluate the efficacy of defect reconstruction using anterolateral thigh (ALT) multiple paddle flaps. The authors performed a retrospective case series of 33 patients who underwent oral and maxillofacial defect reconstruction using the ALT multiple paddle flaps. The design and harvest of the flaps, methods for defects reconstruction, and reconstructive efficacy are described. All 33 patients were men, with a mean age of 49.5 years. Of the flaps, triple skin paddles plus muscle paddles were included in 3 cases, triple skin paddles were included in 1 case, 2 skin paddles plus muscle paddles were included in 29 cases. The skin paddles measured 3×5cm to 10×16cm. Postoperatively, all flaps survived completely. Parotid salivary fistula and orocutaneous fistula occurred in 1 patient of each, thigh wound infection and effusion occurred in 1 and 2 patients, respectively. All patients were followed up for ~2 to 93 months; most patients' oral functions and appearance were acceptable, and thigh motor dysfunction was not observed. With separate skin paddles for defects of different positions, individualized muscle flap for dead spaces, combination of different skin paddles for larger defects, effective reduction or avoidance of wound complications, and acceptable donor site morbidity, the ALT multiple paddle flaps are an ideal candidate for complex oral and maxillofacial defects reconstruction.