PLGA is a suitable biomaterial or polymer for the preparation of novel drug delivery systems due to its biodegradability and biocompatibility. The present review summarized the recent studies on PLGA and its co-polymer-based polymeric nanoparticles. PLGA-based polymeric nanoparticles loaded with different drugs showed effectiveness in their respective therapies. The stealth nanoparticles based on the PLGA co-polymer are developed to overcome the opsonization process during i.v. administration for an improved and targeted drug delivery.