Purpose Most clinical studies on the clinical effects of extracts from Viscum album, the European white-berry mistletoe, focus on the survival of cancer patients, while the effects on the patients’ quality of life (QoL) received less consideration. Thus, we intended to determine the effectiveness of the most commonly used mistletoe extracts which is covered by a large spectrum of published studies, the fermented plant extract Iscador, in the treatment of patients with cancer with respect to QoL-related dimensions. Methods We searched several databases such as PubMed/Medline, Excerpta Medica Database (EMBASE), CAMbase and other. Inclusion criteria were controlled clinical studies on parameters associated with QoL in cancer patients treated with Iscador. Separate search terms were “Iscador” and “study”, “mistletoe” and “study”, and “Viscum” and “study”. Studies were analyzed with respect for trials where patients of the control group received only standard care but no extra treatment. QoL-associated outcome data (mean values and standard deviations, mean/median differences, effect estimates and confidence intervals, odds ratios, etc.) were extracted as they were given in the publication, and converted into standardized mean differences (SMD) and their standard errors using standard formulas. Results We found 13 prospective and controlled studies (9 of them were randomized) that met the inclusion/exclusion criteria and the intended focus on mistletoe extract versus no extra treatment; two additional randomized studies controlled Iscador against placebo/alternative treatment, and thus were not enrolled in the evaluation. The number of patients enrolled varied considerably from 32 to 396. The addressed studies reported positive effects with respect to QoL and related dimension in favor of the Iscador application. A random effect meta-analysis estimated the overall treatment effect at SMD=0.56 (CI: 0.41–0.71, p Conclusion The analyzed studies give some evidence that Iscador treatment might have beneficial short-time effects on QoL-associated dimensions and psychosomatic self-regulation. However, most studies used instruments not appropriate to measure QoL. Thus, well-designed randomized controlled trials with appropriate test instruments are encouraged.