A post-2020 Global Biodiversity Framework is currently under negotiation under the auspices of the Convention on Biological Diversity (CBD). This framework seeks to transform human-nature relationships towards its 2050 vision of “societies living in harmony with nature.” Global reports published to inform these negotiations include the second edition of Local Biodiversity Outlooks (LBO-2). In the context of ethnobiology, LBO-2 is particularly relevant because it features perspectives, experiences, and stories as told by Indigenous Peoples and local communities (IPLC) about the global biodiversity crisis. Based on these perspectives, LBO-2 identifies six areas in need of urgent transformation (i.e., in culture, land, food, economies, governance, and financial incentives), analyzing how these relate to ongoing negotiations of the post-2020 Global Biodiversity Framework. In this article, we consider these transitions, as well as recommendations made by the International Indigenous Forum on Biodiversity, and reveal critical weaknesses in the ways the Global Biodiversity Framework addresses the views and perspectives of IPLC. Such shortcomings include separation of nature and cultures in the framework's goals and targets, and failure to recognize and embed customary land tenure and territorial management as vital for biodiversity conservation, sustainable use, and benefit-sharing. We make a series of recommendations to mainstream and prioritize support for the rights and collective actions of IPLC throughout the post-2020 Global Biodiversity Framework.