Oral mucositis (OM) is a common and often dose-limiting side effect of cancer therapy. Povidone iodine (PVP-I) formulations have been shown to decrease the incidence and severity of OM, but the relevance of these findings remains unclear. The objective of the present study was to review evidence for the use of PVP-I for OM management. An algorithm identified relevant articles published online, and a panel of experts with experience in the management of OM reviewed the findings. Six studies fulfilled the criteria for full review. Two studies provided evidence of moderate quality. Two of the studies with negative findings were confounded by the use of PVP-I concentrations that are too low to be efficacious. The remaining two studies were found to have design flaws. There exists reasonable evidence to support a recommendation for the use of PVP-I in the management of cancer therapy-related OM.