The Periodic Table of the Elements of Green and Sustainable Chemistry (PT-GSC) represents a potentially meaningful tool for teaching and learning Green Chemistry. However, there is a lack of studies exploring the application of the PT-GSC in educational contexts. To contribute to filling this gap, a qualitative and participant approach was developed to examine the effects of using the PT-GSC in a high school setting, with a focus on analyzing the associated challenges and opportunities. Over a five-week period, 23 high school students enrolled in a chemistry course at a public school in Brazil worked in small groups to develop solutions for a case study addressing socio-scientific issues related to water scarcity in the local region using elements from the PT-GSC. Results from both the pre- and post-questionnaires, along with the written case study resolutions, provide evidence of the students’ knowledge gains, particularly in critical scientific literacy for Green and Sustainable Chemistry Education. The findings showed that the PT-GSC is an interdisciplinary tool for introducing students to Green Chemistry concepts within the broader societal and scientific ecosystem. The implementation of novel case studies incorporating elements from the PT-GSC is a way to support our ongoing work with students and the public, contributing to a sustainable future.