The introduction of motorized spiral enteroscopy (mSE) into clinical practice holds diagnostic and therapeutic potential for small-bowel investigations. This systematic review and meta-analysis aims to evaluate the performance of this modality in diagnosing and treating small-bowel lesions. A systematic search of MEDLINE, Cochrane, and ClinicalTrials.gov databases were performed through September 2022. The primary outcome was diagnostic success, defined as the identification of a lesion relative to the indication. Secondary outcomes were successful therapeutic manipulation, total enteroscopy rate (examination from the duodenojejunal flexion to the cecum), technical success (passage from the ligament of Treitz or ileocecal valve for anterograde and retrograde approach, respectively), and adverse event rates. We performed meta-analyses using a random-effects model, and the results are reported as percentages with 95% confidence intervals (CIs). From 2016 to 2022, 9 studies (959 patients; 42% women; mean age >45 years; 474 patients [49.4%] investigated for mid-GI bleeding/anemia) were considered eligible and included in analysis. The diagnostic success rate of mSE was 78% (95% CI, 72-84; I2= 78.3%). Considering secondary outcomes, total enteroscopy was attempted in 460 cases and completed with a rate of 51% (95% CI, 30-72; I2= 96.2%), whereas therapeutic interventions were successful in 98% of cases (95% CI, 96-100; I2= 79.8%) where attempted. Technical success rates were 96% (95% CI, 94-97; I2= 1.5%) for anterograde and 97% (95% CI, 94-100; I2= 38.6%) for retrograde approaches, respectively. Finally, the incidence of adverse events was 17% (95% CI, 13-21; I2= 65.1%), albeit most were minor adverse events (16%; 95% CI, 11-20; I2= 67.2%) versus major adverse events (1%; 95% CI, 0-1; I2= 0%). mSE provides high rates of diagnostic and therapeutic success with a low prevalence of severe adverse events.