With an increasing global population, there is a need for more efficient fertilizers to alleviate the negative environmental impacts of fertilizer runoff. Developments in nanotechnology could lead to fertilizers that interact with plants more efficiently. Aptamers are oligonucleotide receptors that fold into unique shapes and bind target molecules with high affinity and selectivity. Aptamers are generated through the in vitro evolution process called SELEX. Aptamers have been incorporated into sensors, diagnostics, therapeutics, targeted-delivery vehicles, and responsive materials. Biomolecules called exudates that are associated with improved nutrient uptake by crops have been identified and could serve as targets for specific fertilizer delivery. This work describes the selection of DNA aptamers binding to crop exudate, L-serine, for use in a smart fertilizer system. SELEX for small molecules has some inherent challenges, and three SELEX strategies paired with high-throughput sequencing analysis were implemented to improve the selection process. Aptamers developed from an original DNA library, as well as from DNA libraries modified from a previous small molecule selection are described. Aptamers binding to L-serine in solution were identified, and were modified to lower their production cost, and to increase their stability for use in fertilizer applications. Finally, an aptamer-polymersome nanostructure was investigated for potential use as a targeted-delivery vehicle.