The CAD/CAM technology has been increasingly popular in manufacturing spinal braces for patients with adolescent idiopathic scoliosis (AIS) in clinics. However, whether the CAD/CAM-manufactured braces or the CAD/CAM-manufactured braces integrating with biomechanical simulation could improve the in-brace correction angle of spinal braces in AIS patients, compared to the manually manufactured braces, has remained unclear. The purpose of this systematic review and meta-analysis was to compare the in-brace correction angle of (1) computer-aided design and computer-aided manufacturing (CAD/CAM)-manufactured braces or (2) the CAD/CAM-manufactured braces integrating with biomechanical simulation with that of (3) manually manufactured braces. The Web of Science, OVID, EBSCO, PUBMED, and Cochrane Library databases were searched for relevant studies published up to March 2023. Five randomized controlled trials (RCTs) or randomized controlled crossover trials were included for qualitative synthesis, and four of them were included for meta-analysis. The meta-analysis effect sizes of the in-brace correction angle for CAD/CAM versus manual method, and CAD/CAM integrating with biomechanical simulation versus the manual method in the thoracic curve group and the thoracolumbar/lumbar curve group were 0.6° (mean difference [MD], 95% confidence intervals [CI]: −1.06° to 2.25°), 1.12° (MD, 95% CI: −8.43° to 10.67°), and 3.96° (MD, 95% CI: 1.16° to 6.76°), respectively. This review identified that the braces manufactured by CAD/CAM integrating with biomechanical simulation did not show sufficient advantages over the manually manufactured braces, and the CAD/CAM-manufactured braces may not be considered as more worthwhile than the manually manufactured braces, based on the in-brace correction angle. More high-quality clinical studies that strictly follow the Scoliosis Research Society (SRS) guidelines with long-term follow-ups are still needed to draw more solid conclusions and recommendations for clinical practice in the future.