Ankle-foot orthoses (AFOs) are frequently prescribed for children with cerebral palsy (CP) to correct specific features of abnormal gait. However, traditional AFO manufacturing and design involve labor-intensive processes and rely on subjective evaluations of clinicians. Recent advances in three-dimensional (3D) printing allow the rapid prototyping of AFOs, but the expanded design options complicate decision-making. This study aims to evaluate how AFO design affects the mechanical responses of 3D-printed AFOs. The lower limb geometry is established by a 3D-scanning system, and a prototypical AFO is designed, 3D printed, and tested under compression. A parametric study on the effect of base materials, thickness, and trimline location is conducted based on a validated numerical model. The results reveal that AFOs exhibit distinct behaviors under plantarflexion and dorsiflexion motions, with AFO stiffness correlating to thickness through a power function. AFO stiffness is more sensitive to posterior trim depth than inferior, while both trim depths significantly influence stress concentration around the ankle region. This investigation demonstrates the potential of combining 3D printing and computational modeling to improve the design and fabrication process of AFOs, providing insights into the development and customization of 3D-printed AFOs.