Although general practice can contribute to reducing health inequalities, existing evidence provides little guidance on how this reduction can be achieved. We reviewed interventions influencing health and care inequalities in general practice and developed an action framework for health professionals and decision makers. We conducted a realist review by searching MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Cochrane Library for systematic reviews of interventions into health inequality in general practice. We then screened the studies in the included systematic reviews for those that reported their outcomes by socioeconomic status or other PROGRESS-Plus (Cochrane Equity Methods Group) categories. 159 studies were included in the evidence synthesis. Robust evidence on the effect of general practice on health inequalities is scarce. Focusing on common qualities of interventions, we found that to reduce health inequalities, general practice needs to be informed by five key principles: involving coordinated services across the system (ie, connected), accounting for differences within patient groups (ie, intersectional), making allowances for different patient needs and preferences (ie, flexible), integrating patient worldviews and cultural references (ie, inclusive), and engaging communities with service design and delivery (ie, community-centred). Future work should explore how these principles can inform the organisational development of general practice.