: We undertook a systematic review of disease-specific measures of health-related quality of life (HRQL) in diabetic peripheral neuropathy (DPN) to appraise the scientific (psychometric) evidence and make recommendations about the best instrument(s) to use. DPN is a common complication of diabetes mellitus. A need to consider the broad impact of DPN, rather than just pain and the increasingly recognised need to assess patient-reported outcomes such as HRQL in evaluating healthcare has led to a demand for rigorous outcome measures. To identify appropriate disease-specific measures, we searched four databases: PubMed, Embase, PsycINFO and CINAHL Plus. Data were extracted from each article using a standard data extraction form and the psychometric properties of each HRQL measure were reviewed. We identified three DPN-specific measures of HRQL: PN-QOL-97, Norfolk QOL-DN, NeuroQoL. All three measures satisfy at least one criterion for both reliability and validity, though all also have some disadvantages. Where there is no requirement for multi-language versions, the PN-QOL-97 is a useful instrument. Studies that involve multiple languages would need to use the shorter QOL-DN but would also need to incorporate complementary instruments to address the psychological and emotional impact of DPN.