Over the years, issues associated with non-biodegradable polymers have paved the way for biodegradable polymers in the domain of pharmaceutical and biomedical sciences. Poly (lactic-co-glycolic acid) (PLGA) is considered one of the most thrivingly synthesized biodegradable polymers. To formulate polymeric nanostructures, PLGA has attained noteworthy attention due to its controllable properties, complete biodegradability and biocompatibility, well defined formulation techniques and easy processing. This review focuses on fabrication techniques of PLGA based nanostructures and their advanced biomedical applications covering drug delivery and in-vivo imaging. Researchers have extensively investigated the potential of PLGA nanoparticles for target specific and controlled delivery of various micro and macromolecules including drugs, peptides, proteins, monoclonal antibodies, growth factors and DNA in multifarious biomedical applications like neurodegenerative and cardiovascular diseases, inflammatory disorders, cancer and other dreadful health disorders. Beside this, PLGA is being employed for theranostic purposes where polymer is attached with contrast agents for imaging-directed chemo or photo thermal combinative therapy. Multifunctional PLGA nanostructures have given an avenue to future nanomedicine to consider simultaneous drug delivery, molecular imaging, and real-time monitoring of therapeutic response. This review describes the applications of PLGA in drug delivery revealing its current progress and direction for future research.