Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) prevention programmes have been effective in urban residents, their effectiveness in non-urban settings, where cardio-metabolic risk is typically elevated, is unknown. We systematically reviewed the effectiveness of primary prevention programmes aimed at reducing risk factors for CVD/T2DM, including blood pressure, body mass index (BMI), blood lipid and glucose, diet, lifestyle, and knowledge in adults residing in non-urban areas.Twenty-five manuscripts, globally, from 1990 were selected for review (seven included in the meta-analyses) and classified according to: 1) study design (randomised controlled trial [RCT] or pre-/post-intervention); 2) intervention duration (short [<12months] or long term [≥12months]), and; 3) programme type (community-based programmes or non-community-based programmes).Multiple strategies within interventions focusing on health behaviour change effectively reduced cardio-metabolic risk in non-urban individuals. Pre-/post-test design studies showed more favourable improvements generally, while RCTs showed greater improvements in physical activity and disease and risk knowledge. Short-term programmes were more effective than long-term programmes and in pre-/post-test designs reduced systolic blood pressure by 4.02mmHg (95% CI -6.25 to -1.79) versus 3.63mmHg (95% CI -7.34 to 0.08) in long-term programmes. Community-based programmes achieved good results for most risk factors except BMI and (glycated haemoglobin) HbA1c.The setting for applying cardio-metabolic prevention programmes is important given its likelihood to influence programme efficacy. Further investigation is needed to elucidate the individual determinants of cardio-metabolic risk in non-urban populations and in contrast to urban populations.