Neointimal hyperplasia, a pathological response to arterial interventions or injury, often leads to restenosis and recurrent narrowing or occlusion, particularly in the peripheral vasculature. Its prevalence and negative impact on the long-term success of vascular interventions have driven extensive research aimed at better understanding the condition and developing effective therapies. This review provides a comprehensive overview of emerging bioengineering strategies for treating neointimal hyperplasia in peripheral vessels. These approaches include novel therapeutics and cell-based technologies designed to promote re-endothelialization, modulate vascular smooth muscle cell (VSMC) phenotype, reduce inflammation, scavenge reactive oxygen species (ROS), and enhance biomechanical compatibility between grafts and native vessels. Furthermore, advanced therapeutic delivery modalities are highlighted for their potential to achieve targeted, localized treatment at injury sites. This review also explores underrepresented therapeutic targets beyond traditional approaches, offering new opportunities for intervention. The multifaceted examination underscores the challenge of neointimal hyperplasia and presents a promising roadmap toward more effective treatments, ultimately aiming to improve patient outcomes after vascular interventions.