The major problem in peripheral nerve repair is restoration of the microenvironment rather than traditional structural reconstruction. Nanodiamonds (NDs), highly biocompatible carbon nanoparticles, are widely applied in medical engineering. They may alleviate inflammatory insults in peripheral nerve injury because they can induce macrophage polarization from a proinflammatory to an anti-inflammatory state. Here we report a concentric multilayered spraying manufacturing process to fabricate microporous ND/polycaprolactone (PCL) nerve bridges. We investigated the proliferative, adhesive, and glioprotective role of these bridges in Schwann cells in vitro. We further evaluated their long-term in vivo performance in a 20-mm sciatic nerve defect rat model. ND/PCL nerve bridges are comparable to autografts in functional, electrophysiological, and morphological sciatic nerve repair. They ameliorate the immune milieu by inducing M1 to M2 macrophage polarization. In addition, they pose no harm to major organs after 4 months of implantation. These findings show the promising roles of ND-based nanotechnology in neuroengineering.