Aim: To review clinical evidence regarding the effectiveness, safety, and practical implications of custom-made 3D-printed ankle-foot orthoses in individuals with lower limb impairments. Materials and Methods: A structured literature review was conducted through PubMed and the MAUDE adverse event database. Studies were included if they investigated custom-made 3D-printed mechanical AFOs and reported outcomes related to clinical effectiveness or safety. A total of 278 records were identified; after two-stage screening, 17 studies met the inclusion criteria. Conclusions: Custom-made 3D-printed AFOs represent an effective and safe solution for individualized management of lower limb impairments. Evidence from 17 studies demonstrates improvements in gait kinematics, plantar pressure distribution, spatiotemporal parameters, and patient satisfaction, with outcomes equivalent to conventionally manufactured devices. No serious adverse events were identified. Future research should prioritize large-scale randomized controlled trials with standardized outcome measures and longer follow-up periods.