A trauma-informed approach is a framework for organisational (synonym system) change interventions that address the universal prevalence and impact of trauma. This mixed methods systematic review assessed the effects of trauma-informed approaches on psychological, behavioural, and health outcomes in health-care providers and adult patients in primary care and community mental healthcare. We searched five databases and grey literature and consulted experts for reports published in January 1990 to June 2021. The quantitative descriptive and qualitative framework syntheses were integrated through a line of argument and mapped onto a logic model. We included six nonrandomised studies that evaluated eight interventions with varied theoretical developments, components, and outcomes. The most common components were budget allocation, workforce development, identification/response to violence and trauma, and evaluation. Evidence for intervention effects was limited and conflicting. Four studies reported improvement in provider readiness and sense of community, while three reported conflicting effects on provider behaviour regarding delivery of trauma-informed care. Four studies reported some improvement in patient readiness for disease management and access to services; however, the evidence for patient satisfaction was conflicting. Two studies found that patients and providers felt safe. While one study reported improvement in patient quality of life and chronic pain, another found no effect on substance use, and three studies reported conflicting effects on mental health. Intervention mechanisms included a package of varied components, tailoring to the organisational needs, capacities and preferences, staff education and self-care, creating safe environments, and shared decision-making. Intervention effects were moderated by contextual (health system values, policies, governance, business models, trauma-informed movement, organisational culture, and social determinants of health) and intervention factors (buy-in from all staff, collective learning through conversations, equal attention to staff and patient well-being, and sustainable funding). No studies measured adverse events/harm, cost effectiveness, or providers’ health. We need more methodologically robust evaluations of trauma-informed organisational change interventions.