Importance: Type 2 diabetes is common and is a leading cause of morbidity and disability. Objective: To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, -1.7 mm Hg [95% CI, -2.6 to -0.8] and -1.2 mm Hg [95% CI, -2.0 to -0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Conclusions and Relevance: Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.