Aim
Exercise therapy is a core element in the treatment of diabetes, but the benefits and harms for patients with a diabetic foot ulcer (DFU) are unknown. We therefore aimed to systematically review the benefits on health-related quality of life (HRQoL) and harms of exercise therapy for patients with DFU.

Methods
We searched 6 major databases. We performed citation and reference searches of included studies and contacted authors of ongoing trials. We included randomized controlled trials (RCTs) to assess potential benefits on HRQoL and harms of exercise therapy. Observational studies were included to identify potential harms of exercise therapy.

Results
We included 10 published publications of 9 trials and results from 2 unpublished trials including a total of 281 individuals with DFUs receiving various forms of exercise therapy. Due to lack of HRQoL measurements and high heterogeneity, it was not possible to perform meta-analyses. Results on HRQoL was present in one unpublished study. Harms reported ranged from musculoskeletal problems, increased wound size, to amputation; however, no safe conclusions could be drawn from the available data due to high heterogeneity and risk of bias in the trials.

Conclusions/Interpretation
Protective strategies are often preferred over therapeutic exercise that might have unforeseen consequences for patients over time. Based on the current literature, no evidence-based recommendations can be provided on the benefits and harms of exercise therapy for patients with DFUs. Well-conducted RCTs are needed to guide rehabilitation including detailed description of adverse events and an exercise program in a semisupervised or fully supervised setting.