For millennia humans have extracted biological and physical resources from the planet to sustain societies and enable the development of technology and infrastructure. Growth in the human population and changing consumption patterns have increased the human footprint on ecosystems and their biodiversity, including in fresh waters. Freshwater ecosystems and biodiversity face many threats and it is now widely accepted that we are in a biodiversity crisis. One means of protecting and restoring freshwater biodiversity is to better manage the exploitation of freshwater biota and aggregate resources (e.g., sand, gravel, and boulders). Here we outline the threats arising from such exploitation and identify response options to ensure that methods and levels of extraction are sustainable and allow recovery of over-exploited freshwater biodiversity and ecosystems. The guidance we provide will enable practitioners, policy-makers, and resource stewards to embrace effective, sustainable, and evidence-based approaches to resource extraction. Response options for managing species exploitation include strengthening assessment and reporting, using science-based approaches to reduce overexploitation and support recovery, embracing community engagement, and building or tightening legislation. Response options for managing exploitation of freshwater aggregate resources include reducing demand for harvest, strengthening governance, reporting, and monitoring of environmental impacts, and promoting the restoration of degraded ecosystems or compensating for losses. Diverse case studies highlight examples of where various management actions have been implemented in an effort to consider how they can be scaled up and adapted to other contexts. Managing exploitation will be a key aspect of broader initiatives needed to protect and restore freshwater biodiversity around the globe.