The functionalization of nanoparticles with specific ligands, such as antibodies, peptides, and small molecules, plays a critical role in achieving targeted delivery, enhancing biocompatibility, and controlling drug release. However, to date, practically no attention has been paid to the design of green ligands. Herein, an innovative approach to develop a sustainable ligand for nanoparticle functionalization is reported. Its synthesis involved a photochemical thio-ene “click” reaction between the natural compounds phosphatidylcoline, the main component of lecithin, and cysteine, followed by a reductive amination with mannose, a sugar of growing interest for biomedical targeting, in a continuous flow hydrogenation reactor. Comprehensive characterization techniques, including nuclear magnetic resonance (NMR), mass spectrometry (MS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and elemental analysis, confirmed the structure and properties of the novel ligand. The environmental sustainability of the ligand was evaluated determining some green metrics using the EATOS software. The obtained E-factor was compared with a conventional PEG-based ligand. The newly developed lecithin-derived ligand was successfully used to functionalize diverse NP platforms, including the MOFs MIL-101(Fe), PCN-222, UiO-66, and iron nanoparticles (in the form of akaganeite), demonstrating its potential in nanomedicine applications., Financial support was provided by the Andalusian Ministry of Economy, Science and Innovation in the framework of the Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020, programme 54ª “Investigación científica e innovación”, “POSTDOC_21_00594”), the Spanish Ministry of Science and Innovation (Ref: PID2020-119949RB-I00), the Andalusian Ministry of Economy, Science and Innovation cofinanced by the European Regional Development Fund (ERDF) from FEDER and the European Social Fund (ESF) (PY20_00882 and CV20-04221). The COST action CA-18132 “Functional Glyconanomaterials for the Development of Diagnostic and Targeted Therapeutic Probe” is also acknowledged. The COST action CA-22147 “European metal–organic framework network: combining research and development to promote technological solutions” (EU4MOFs) is also acknowledged., Peer reviewed