This study systematically analysed peer-reviewed publications describing validation aspects of the Dermatology Life Quality Index (DLQI) and used Naicker’s Critically Appraising for Antiracism Tool to assess risk of racial bias. Seven online databases were searched from 1994 until 2022 for articles containing DLQI validation data. Methodology followed PRISMA guidelines, the protocol was registered in PROSPERO, and articles reviewed independently by two assessors. Of 1,717 screened publications, 207 articles including 58,828 patients from > 49 different countries and 41 diseases met the inclusion criteria. The DLQI demonstrated strong test–retest reliability; 43 studies confirmed good internal consistency. Twelve studies were performed using anchors to assess change responsiveness with effect sizes from small to large, giving confidence that the DLQI responds appropriately to change. Forty-two studies tested known-groups validity, providing confidence in construct and use of the DLQI over many parameters, including disease severity, anxiety, depression, stigma, scarring, well-being, sexual function, disease location and duration. DLQI correlation was demonstrated with 119 Patient Reported Outcomes/Quality of Life measures in 207 studies. Only 15% of studies explicitly recruited minority ethnic participants; 3.9% stratified results by race/ethnicity. This review summarizes knowledge concerning DLQI validation, confirms many strengths of the DLQI and identifies areas for further validation.