INTRODUCTION: Lay-caregivers in organ transplantation (to candidates, recipients, and donors) are essential to pre- and post-operative care, but report significant caregiving-related stressors. This review aims to summarize studies testing non-pharmacological interventions aimed at improving organ transplant caregiver-reported outcomes. METHODS: In accordance with PRISMA, we conducted a systematic review (searched PubMed, Embase, Cochrane Central, PsycInfo, and CINAHL, no start-date restriction through 7/1/2021). Quality of comparative studies assessed by ROBS-2 or ROBINS. RESULTS: Twelve studies met inclusion. Study designs, interventions, and outcomes varied. Sample sizes were small across caregivers to adult (nine studies, five with caregiver samples) and pediatric patients (three studies, caregiver samples). Study designs included seven single-arm interventions, two pre-post with comparison cohorts, and three randomized-controlled trials. Eight studies included transplant-specific education as the intervention, an interventional component, or as the comparison group. Outcomes included transplant specific knowledge, mental health, and intervention acceptability. Of the nine pre-post caregiver assessments and/or comparison groups, four studies demonstrated no statistically significant intervention effects. CONCLUSION: Few interventions addressing the needs of organ transplant caregivers have been empirically evaluated. Existing interventions were well-received by caregivers. Given complexities of care in transplantation, research is needed evaluating interventions using rigorous trial methodology with adequate samples.