There have been consequences regarding the increment of the greenhouse effect, such as the rise in the planet’s global temperature, and climate change. Refrigerants have an important contribution to the aforementioned environmental impact. In particular, hydrofluorocarbons (HFCs) contribute to the destruction of the ozone layer and the increase of the greenhouse effect. Protocols, international agreements, and legislation were developed to slow down the emission of greenhouse gases. Prohibition and definition of deadlines for the gradual elimination of various refrigerants have been proposed to replace them with others that are environmentally sustainable. Soon, the refrigeration sector will have to replace some refrigerants with others that are alternative and/or sustainable with minimal or zero environmental impact. A computational tool to support decision-making regarding the selection of alternative and/or sustainable refrigerant to replace the old one is developed to be used by refrigeration companies, manufacturers, and installers. A suggestion of refrigerants with reduced environmental impact is provided, ensuring similar thermal performance and energy efficiency, considering the safety level and renovation cost of the installation and refrigerant itself. This decision support system (DSS) uses an objective function that includes the technical specifications and properties of alternative and sustainable refrigerants. The computational tool is applied in the agri-food sector in three case studies. The results show not only the consistency of the computational tool, but also its flexibility, objectivity, and simplicity. Its use allows companies to choose refrigerants with reduced environmental impact, reduced or zero ozone depletion potential and global warming impact, thus contributing to environmental sustainability.