Rutin, a natural flavonol glycoside is known to possess significant radical scavenging properties which might have beneficial effects in cerebral ischemia. However its oral administration and pharmaceutical use is limited due to its poor aqueous solubility and bioavailability. The current investigation aimed at development of rutin–phospholipid complexes (Ru–PLC's) and its characterization to provide neuro-protective effects in brain injury following stroke. Ru–PLC's were successfully fabricated and findings demonstrated improvement in bio-pharmaceutical properties on the basis of solubility, partition coefficient, dissolution profile, morphology, zeta potential, physical stability, FT-IR, DSC-TGA, forced degradation, photolytic degradation, ROS detection and oral pharmacokinetic studies. Ru–PLC's considerably improved functional outcomes in experimental stroke (MCAO model in rats) at a dose less than half of the effective dose of rutin. Effectiveness of treatment as evident from pharmaceutical properties as well as therapeutic activity was of the following order: Ru–EPLC > Ru–TPLC > rutin.