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A systematic review and meta-analysis were carried out to investigate the effect of ultrasound-assisted wound (UAW) debridement in patients with diabetic foot ulcers (DFUs). All selected studies were evaluated using the Cochrane risk of bias tool to assess the risk of bias for randomized controlled trials. PubMed and Web of Science were searched in October 2021 to find randomized clinical trials (RCT) assessing the effect of UAW debridement on DFUs. RevMan v5.4. was used to analyze the data with the Mantel–Haenszel method for dichotomous outcomes. A total of 8 RCT met our inclusion criteria, with 263 participants. Concerning the healing rate comparing UAW versus the control group, a meta-analysis estimated the pooled OR at 2.22 (95% CI 0.96–5.11, p = 0.06), favoring UAW debridement, with low heterogeneity (x2 = 7.47, df = 5, p = 0.19, I2 = 33%). Time to healing was similar in both groups: UAW group (14.25 ± 10.10 weeks) versus the control group (13.38 ± 1.99 weeks, p = 0.87). Wound area reduction was greater in the UAW debridement group (74.58% ± 19.21%) than in the control group (56.86% ± 25.09%), although no significant differences were observed between them (p = 0.24). UAW debridement showed higher healing rates, a greater percentage of wound area reduction, and similar healing times when compared with placebo (sham device) and standard of care in patients with DFUs, although no statistically significant differences were observed between groups.