Indigenous knowledge, a multidimensional framework of know¬ledge system passed down from genera¬tion to generation, provides a valuable but often neglected tool in addressing global challenges. Such understanding, rooted in millennia of cultural, environmental, and spiritual traditions, fosters sustainable livelihoods, resilient communities, and social harmony. In an era of ecological crises, climate change, and growing divisions between rich and poor amidst the promise of rapid technological advancement, incorporating indigenous wisdom into innovation processes offer an opportunity for deep system change that can create effective, impactful, sustainable solutions. However, the place of indigenous knowledge within global systems of entrepreneurship and innovation presents both opportunities and challenges worthy of engagement. This paper explores how indigenous knowledge can be integrated in a manner beyond a Western paradigm; something that would be valuable to global innovation in sustainable development, biodiversity strategies, and social entrepreneurship. Through archival documents and specific case studies of indigenous knowledge applications in environmental management and community-driven business models, the paper illustrates a mutualistic relationship between traditional practices at local levels and modern science and technology. Agroforestry and crop diversification, for instance, are indigenous agricultural practices that provide sustainable methods of producing food as alternative models to industrial agriculture. Traditional medicinal knowledge has also played a complementary role in the progress of pharmaceutical products by introducing novel natural agents that can potentially be used as therapeutic agents. Indigenous governance systems, with their emphasis on communal well-being and sustainability for future generations, offer ethical frameworks for social entrepreneurship that can engender more equitable models of doing business around the world. Despite the potential benefits, there are challenges. For instance, incorporating indigenous knowledge raises the concern in intellectual property of whether indigenous communities would be acknowledged as legitimate source of innovation. The paper advocates a holistic approach in collaboration and promotion of indigenous knowledge towards a more inclusive innovation and sustainable development for the overall benefit of the global population.