Compassion-based interventions show promise in enhancing well-being and reducing distress, but little is known about their applications for people with long-term physical conditions. This study explores compassion-based interventions for this population: what are their differing elements (content, structure, tailoring, use of technology), feasibility and acceptability, effects and experienced benefits? A mixed-methods systematic review was conducted. Four bibliographic databases were searched without study design restrictions. Meta-synthesis was used to integrate quantitative results of effects and qualitative results of experienced benefits. Twenty studies met the inclusion criteria. Most studies targeted people with cancer or persistent pain. Interventions were either comprehensive with 6-12 face-to-face sessions, or brief based on a single compassion exercise. Feasibility and accessibility were highly rated by participants. Amongst a plethora of outcomes, reductions in depression and anxiety were the most common findings. Our qualitative synthesis yielded experienced benefits of (1) acceptance of the condition; (2) improved emotion regulation skills; (3) reduced feelings of isolation. There was minimal overlap between quantitative and qualitative outcomes. While the field is still in its infancy, this review highlights the potential benefits of compassion-based interventions for people with long-term physical conditions and discusses recommendations for further intervention research and development.