Polymeric biomaterials are found to have extensive applications in nanomedicine mainly for delivery of drugs and tissue engineering-regenerative applications. Poly(lactide-co-glycolic acid) (PLGA), in particular, has been efficiently utilized for its synthetic plasticity, biocompatibility, and most importantly its FDA approval status. In the past two decades, PLGA has been among the widely used polymeric materials to fabricate devices for the controlled/sustained/targeted delivery of small molecules, proteins, DNA/RNA/peptide molecules as well as other tissue engineering applications. Hybrid-type nanocomposites have also emerged as an enthusiasm for drug delivery system development with flexible physical and chemical properties that have explicit therapeutic potential and minimal side effects. There are some commercially available PLGA products, but the available systems still have many defects due to their development and manufacturing, such as wide size distribution and issues with drug stability. New advances and optimizations in the previous studies could bring a new path of “smart tools” in the development of personalized, noninvasive emerging nanomedicine.