Though innovations for sustainable management of natural resources have emerged over time, the rising demand for nature based health solutions and integration of endemic flora into global value chains could have adverse impacts on ecosystems. The ecological risks in the exploitation of wild medicinal plant resources are exacerbated by a myriad of agrotechnological risks and challenges that highly constrain their domestication. Successful exploitation and commercialization of medicinal plants thus require a clear understanding of their demand and production systems or value chain analysis. Accordingly there is need for innovative approaches towards their integration into global value chains. Since quality and safety, traceability, certification, as well as, consumer tastes and preferences are critical drivers in purchasing decisions by global consumers, they are inadvertently exploited to weaken Indigenous knowledge (IK), undermine common property rights and entrench value chains that favour a few elite buyers. This tend to create pervasive incentives for overexploitation of medicinal plant resources and environmental degradation. Potential solution lies in the recognition of drivers of vulnerability to environmental degradation and the innovative use of policy bricolage, feedback loops and interactions between knowledge, power and agency on one hand, and collective action and property rights institutions on the other hand. We conceptualise a framework that can mediate a transformational agenda and enhance systematic understanding of sustainability lenses in endemic medicinal plant resources value chains. This could in turn strengthen IK, enhance collective action and promote participation of local actors with positive impact on the utilisation and integration of endemic medicinal plant resources into global value chains.