BackgroundOffloading treatment is crucial to heal diabetes‐related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU.MethodsWe searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight‐bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost‐effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta‐analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed.ResultsFrom 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non‐controlled), 35 meta‐analyses performed, and 128 evidence statements developed. We found non‐removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09–1.41; N = 14, n = 1083), and may increase adherence, cost‐effectiveness and decrease infections, but may increase new lesions. Removable knee‐high offloading devices may make little difference to ulcers healed compared to removable ankle‐high offloading devices (RR 1.00, 0.86–1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89–2.18; N = 5, n = 235) and cost‐effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05–5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97–1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers.ConclusionsNon‐removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non‐surgical offloading interventions to heal most plantar DFU. However, all these interventions have low‐to‐moderate certainty of evidence supporting their outcomes and more high‐quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.