Young people continue to experience high rates of loneliness that peaked during the global pandemic, exacerbated by uncertainty about their life purpose alongside climate change anxiety. In these uncertain times, it is essential to empower younger generations with hope and equip them with creative competencies to help create solutions for a better environmental and social future. This chapter will discuss the process of—and research basis for—developing an effective teaching practice based on the Indigenous wisdom of our connection to the Earth, plant and soil ecology, and student empowerment through the lens of the permaculture design framework. Before European arrival on Turtle Island (North America), Indigenous people were taking care of its ecosystems, and with their wisdom, developed an Indigenous scientific method based on symbiotic relationships between plants to ensure food security while maintaining healthy soil ecology. In this chapter, we explore the intersection and complementarity between Indigenous and Western science. We elaborate on the foundation of a plant guild and the integrated, ecological design approach in permaculture. Corn, beans and squash, known as the Three Sisters growing together, are an example of a traditional Haudenosaunee gardening practice that students are invited to explore firsthand in the curriculum. We also present the theoretical background to develop students’ agency, and its continuum along this teaching activity. Our pedagogical practice in science, technology and environmental education interweaves Indigenous and Western science, and can be adapted for different areas in North America. Our intention in designing this minds-on, hands-on curriculum is to support teachers in their efforts to engage and teach young people to understand their co-dependence with Nature.