--- - |2+ Abstract Objectives The objectives of this systematic review were to (a) identify supportive‐care (psychosocial/behavioral, pharmacological, complementary, or alternative) interventions that have been evaluated via randomized controlled trials (RCTs) to improve patient‐reported health‐related quality of life (HRQoL) among adults with brain tumors, (b) evaluate the quality of the intervention studies, and (c) evaluate if developed interventions have been efficacious at improving HRQoL, as compared with control conditions in RCTs. Methods This systematic review was conducted using preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. Four databases were searched for RCTs of supportive‐care interventions for adults with brain tumors, primary or metastatic, that included a patient‐reported HRQoL outcome. Quality of the included studies was assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Results Ten RCTs involving 640 patients with either a primary or metastatic brain tumor investigating supportive‐care interventions with a HRQoL outcome were identified. In terms of quality, three of the studies received a “strong” rating, three received a “moderate” rating, and four of the studies received a “weak” rating. Only two of the interventions (ie, a home‐based psychosocial intervention and individualized acupuncture with standard rehabilitation) demonstrated improvements in HRQoL over control conditions. Conclusions HRQoL is of the utmost importance when treating patients with brain tumors. Yet there is a notable paucity of research to inform clinical decisions and evidence‐based practice. More high‐quality studies of interventions aimed at improving HRQoL are needed. - Psycho-Oncology, EarlyView.