Objectives: A wide range of non-clinical nature and culture-based interventions for the treatment of health issues have been evaluated in evidence and systematic reviews. However, common outcomes of these interventions have not been identified and neuro-bio-psychosocial mechanisms underlying how these interventions impact health are not well understood. We conducted a systematised review and compare the evidence for human responses to nature and culture-based non-clinical interventions for a range of health issues and assess the proposed mechanisms and conceptual frameworks underlying these interventions.Design: Comprehensive searches were conducted up to May 2018 in six bibliographic databases: Campbell Collaboration, Cochrane Library, Embase, Medline, Scopus and Web of Science. Studies included were evidence reviews or systematic reviews on any nature or culture-based non-clinical intervention to improve the health of individuals. Results: 60 reviews were included (33 of nature, 26 of culture, 1 of both) covering 1480 individual studies and trials. The most commonly investigated health outcomes included: general physical health (14 studies), mental health and wellbeing (9), Alzheimer’s and dementia (7), cancer (7), dietary behavior (5), aging (3) and schizophrenia (3). The most common review types were systematic reviews (32), literature reviews (22) and meta-analyses (7). A range of outcomes were common to both nature and culture-based interventions including physical activity, social interaction, stimulation, relaxation, skills development, and positive impact of the intervention environment. Only two reviews proposed conceptual frameworks and the neuro-bio-psychosocial mechanisms that underpin the health changes were not clarified. Conclusions: Future research should focus on reviewing the evidence gaps for non-clinical nature and culture-based interventions with an emphasis on implementing larger sample sizes, cohort and longitudinal studies, which deploy a wider range of mixed methods, quasi-experimental and Randomised Control Trials. There should also be agreement on terminology and developing conceptual frameworks to better understand the neuro-bio-psychosocial mechanisms underlying interventions.