Three-dimensional (3D) printing technology enables designers to push the limits of their creativity, creating new possibilities for high-performance footwear. With advancements in engineering and a deeper understanding of biomechanics, researchers have designed footwear with complex structures comprising various materials. These materials and structures exhibit diverse physical properties and are used in physical activity, sports rehabilitation and competitive athletics. This article offers a systematic review of the biomechanical responses to advancements in 3D-printed footwear research from the past decade, focusing on three key domains: injury prevention, comfort, and athletic performance. Current research suggests that adjusting material stiffness or incorporating specific design elements in 3D-printed footwear can modulate plantar pressure distribution, which plays a crucial role in injury prevention, while also enhancing comfort. However, a consensus has yet to be reached regarding the impact of such footwear on athletic performance. Owing to the heterogeneity of research methodologies, the effectiveness of these designs may be significantly influenced by the design specifics, materials used, and individual user differences. Further systematic research and long-term clinical trials are crucial to advancing this field.