The deep peroneal nerve (DPN) is considered one of the clinically significant nerves of the lower extremity since several clinical abnormalities can commonly be caused by its defects, either in its sensory or motor functions. Its derivatives, classified as muscular, cutaneous, and articular, mainly supply the muscles in the anterior fascial compartment of the leg and the dorsum of the foot, the 1st dorsal web space of the foot, the ankle joint, and certain joints of the foot. To improve the effectiveness of clinical practices involving the DPN, it is important to first understand its anatomical nature, including its typical characteristics and the variants (orientation, branching, and analogous structure), prior to applying such practices in clinical implementation. This review, therefore, aims to review the previously studied information of DPN on its fundamental anatomy and link it to the provided examples of current commonly used procedures, both non-invasive and invasive, e.g., nerve imaging, nerve block, neuroelectrophysiological study, and free autologous tissue transfer, thereby giving an integrated view in the translational medicine of DPN. Conclusively, the ultimate goal of this review is to help maximize the therapeutic effectiveness and to minimize the unanticipated complications of any clinical practices involving the DPN by inferring from its anatomical knowledge.