Uranium plays a pivotal role in nuclear energy production, and extracting it from seawater offers a promising solution to alleviate shortages in land-based uranium resources. However, the marine environment with ultra-low uranium concentrations, high salinity, and microbial activity poses significant extraction challenges, compounded by selectivity and cost limitations in current methods. In the present investigation, an anti-biofouling amino oxime-functionalized collagen/sodium alginate aerogel (CF-AO/SA) was fabricated using leather waste-derived collagen. The dual cross-linked CF-AO/SA network, enhanced by Zn2⁺ incorporation, showed improved structural stability and antibacterial properties, as well as high uranium adsorption capacity, selectivity, and reusability. It achieved 320.7 mg g−1 in 14 ppm uranium solution and maintained 78.6% removal efficiency after five cycles. Additionally, the removal rate of uranium was 89% in simulated seawater. Field tests in Zhuhai's Jinwan District (113.35° E, 21.99° N) showed 5.16 mg g−1 uranium adsorption and excellent mechanical strength after 30 days in seawater. Furthermore, the production cost of CF-AO/SA was estimated at $3.652 per kilogram, which is lower than other reported adsorbents. The newly developed bio-based aerogel beads have substantial potential for practical applications for uranium capture in seawater and provide a novel high-value utilization way for leather wastes. Graphical Abstract