Nonobvious controlled polymeric pharmaceutical excipient, chitosan nanoparticles (CS-NPs) for lenalidomide encapsulation were geared up by the simple ionic cross linking method to get better bioavailability and to reduce under as well as overloading of hydrophobic and sparingly soluble drug lenalidomide towards cancer cells. Lenalidomide loaded chitosan nanoparticles (LND-CS-NPs) were in the size range of 220–295 nm and characterized by DLS, TEM, FT-IR, TGA and XRD. Encapsulation of lenalidomide over chitosan nanoparticles was observed about 99.35% using UV spectrophotometry method. In vitro release and the cytotoxic studies were performed using LND-CS-NPs. This study implies the new drug delivery route for lenalidomide and illustrates that the CS-NPs serves as the effective pharmaceutical carrier for sustained delivery of lenalidomide.