Aim and objective: To fabricate a customized intraoral prosthesis (IOP) and determine its dosimetric, clinical, and economic impact in oral cancer patients undergoing radiation therapy (RT). Materials and methods: Intraoral prosthesis was made using routine chairside and laboratory techniques using alginate, dental stone, and heat cure acrylic resin. Modifications in the IOP were made according to the specific case. Six patients with head and neck cancers (HNC) involving either of the jaws, planned to receive either adjuvant or definitive RT with the presence of one or more risk factors of developing severe acute radiation-induced toxicities were enrolled in this study. Results: With the use of a customized IOP during radiation treatment, an improvement in radiation-induced oral mucositis (RIOM) was observed from grade III to grade I. There was a significant reduction in the radiation dose received by normally involved structures of the oral cavity. The minimal cost of the fabrication of IOP negates the cost involved in the management of severe grade RIOM and its complications. Conclusion: Fabrication of a low-cost customized IOP in oral cancer patients undergoing RT is feasible and its use with modern techniques of RT planning and delivery can reduce the doses to the normal tissues in the oral cavity, thereby reducing the severity of RIOM in patients with cancers of the oral cavity. Clinical significance: Radiation therapy has significant acute side effects like mucositis, oral ulceration, and impaired taste, which increases morbidity leading to multiple breaks in the treatment. Also, the negative psychological impact of these side effects causes them to discontinue the treatment, thus worsening the disease outcome. We present a study on the fabrication of a custom-made, and affordable IOP and its efficacy in decreasing the severity of acute side effects of RT.