Nanosized lipid vesicles are ubiquitous in residing techniques (e.g. mobile compartments or extracellular vesicles, EVs) and in formulations for nanomedicine (e.g. liposomes for RNA vaccine formulations). The mechanical properties of such vesicles are essential in a number of physicochemical and organic processes, starting from mobile uptake to stability in aerosols. Nonetheless, their correct willpower stays difficult and requires refined devices and knowledge evaluation. Right here we report the primary proof that the floor plasmon resonance (SPR) of citrated gold nanoparticles (AuNPs) adsorbed on artificial vesicles is finely delicate to the vesicles’ mechanical properties. We then leverage this discovering to indicate that the SPR monitoring offers quantitative entry to the stiffness of vesicles of artificial and pure origin, corresponding to EVs. The demonstration of this plasmon-based “stiffness nanoruler” paves the way in which for growing a facile, cost-effective and high-throughput methodology to assay the mechanical properties of dispersions of vesicles of nanometric measurement and unknown composition at a collective degree.