The orexigenic peptide ghrelin is involved in various and vital physiological processes such as food uptake, regulation of body weight and glucose metabolism. At Ser3 ghrelin is modified with a fatty acid. This unique posttranslational modification renders ghrelin active to bind to the growth hormone secretagogue receptor (GHSR)1a whereas deacylated ghrelin is inactive. The L-aptamer NOX-B11 was identified to specifically bind and neutralize octanoylated, i.e. active ghrelin. L-aptamers (also termed Spiegelmers) are oligonucleotide binders built from non-natural L-nucleotides that confer resistance to nucleases. Dynamic light and X-ray scattering measurements were applied to learn more about the specific recognition of a fatty acid modification by an oligonucleotide. First data revealed that upon ghrelin binding NOX-B11 undergoes a conformational change resulting in a 1:1 Ghrelin•NOX-B11 complex. Furthermore, crystals of Ghrelin•NOX-B11 were obtained and optimized by multiple cycles of micro seeding. X-ray diffraction data were collected from a single crystal to a resolution of 2.65 Å and the space group was determined to be C2. The Matthews coefficient was calculated to be 2.75 Å3Da−1, corresponding to a solvent content of approx. 60%.