The goal of this project was to create and optimize the performance of portable chambers for reliable ultraviolet (UV) disinfection of personal protective equipment (PPE) and enable its safe reuse. During unforeseen times of high demand for PPE, such as during the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), single-use PPE supply can be quickly depleted. UV radiation has been shown to disinfect materials with high efficacy. This paper reports the design and construction of two 280 nm ultraviolet-C (UV-C) disinfection chambers in the form of portable chambers with 46 cm × 46 cm × 46 cm interior dimensions, one using light-emitting diodes and the other using mercury vapor lamps. This paper summarizes and presents a review of SARS-CoV-2 UV deactivation research during 2020 to 2021. Additionally, this paper discusses efforts to increase the uniformity and overall intensity of the UV-C radiation within the chambers through the installation of a UV-reflective, porous polytetrafluoroethylene (PTFE) material. A calculator prototype was additionally designed to calculate the reduction of SARS-CoV-2 as a result of UV-C disinfection, and the prototype code is presented. The paper describes the selection of UV-C radiation sources for the chambers and the chambers’ mechanical and electrical design, PTFE installation, testing, and safety considerations.