BackgroundPsychological distress is common in patients with cancer; interfering with physical and psychological wellbeing, and hindering management of physical symptoms. Our aim was to systematically review published evidence on non-pharmacological interventions for cancer-related psychological distress, at all stages of the disease.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered on PROSPERO (CRD42022311729). Searches were made using eight online databases to identify studies meeting our inclusion criteria.Data were collected on outcome measures, modes of delivery, resources and evidence of efficacy. A meta-analysis was planned if data allowed. Quality was assessed using the Mixed Methods Appraisal Tool (MMAT).ResultsFifty-nine studies with 17,628 participants were included. One third of studies included mindfulness, talking or group therapies. Half of all studies reported statistically significant improvements in distress. Statistically significant intervention effects on distress were most prevalent for mindfulness techniques. Four of these mindfulness studies had moderate effect sizes (d= -0.71[95% CI: -1.04, -0.37]p<0.001) (d= -0.60 [95% CI: -3.44, -0.89]p<0.001) (d= -0.77 [CI: -0.146, -1.954]p<0.01) (d= -0.69 [CI: -0.18, -1.19]p=0.008) and one had a large effect size (d= -1.03 [95% CI: -1.51, -0.54]p<0.001). Heterogeneity of studies precluded meta-analysis. Study quality was variable and some had a high risk of bias.ConclusionsThe majority of studies using a mindfulness intervention in this review are efficacious at alleviating distress. Mindfulness—including brief, self-administered interventions—merits further investigation, using adequately powered, high-quality studies.Systematic review registrationThis systematic review is registered on PROSPERO, number CRD42022311729.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12904-023-01202-8.