Objective To observe the effect of ultrasonic debridement machine (UDM) combined with vacuum sealing drainage (VSD) in diabetic foot (DF) ulcer healing. Methods A total of 153 cases with DF ulcer were divided into VSD+UDM group (n = 77) and VSD group (n = 76) according to the order of admission. The bacterial clearance rate, wound surface, wound surface reduction, wound surface reduction rate and other related index were compared. Results The bacterial clearance rate, wound surface reduction and wound surface reduction rate were higher, while wound surface was lower in VSD+UDM group than in VSD group (P < 0.05 or P < 0.01). The surface healing time, dressing times and hospital stays were lower in VSD+UDM group than in VSD group (P < 0.05 or P < 0.01). There was no statistical significance on transcutaneous oxygen pressure before treatment, and compared with VSD group, the transcutaneous oxygen pressure was reduced after treatment. Conclusion UDM combined with VSD in DF ulcer healing can promote wound healing, reduce the healing time, hospital stays and hospitalization costs. The treatment effectiveness of UDM+VSD is more prominent than traditional treatment combined with VSD.