Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable and biocompatible copolymer in drug delivery systems (DDSs). This article highlights the critical physicochemical properties of PLGA, including molecular weight, intrinsic viscosity, monomer ratio, blockiness, and end caps, which significantly influence drug release profiles and degradation times. The review covers extensive literature on the application of PLGA in delivering various types of drugs, such as small-molecule drugs, proteins, peptides, antibiotics, and antiviral drugs. PLGA-based DDSs have shown promise in treating various diseases, including cancer, neurological disorders, pain, and inflammation. Incorporating drugs into PLGA nanoparticles and microspheres enhances therapeutic efficacy, reduces toxicity, and improves patient compliance. The article also discusses the latest research on PLGA applications, including innovative formulation techniques and stimuli-responsive formulations. Additionally, it explores the development of PLGA-based delivery systems for combination therapy and hybrid systems that combine PLGA with other polymers or biomaterials. The article provides detailed examples of PLGA-based DDSs in action, such as in pain management, cancer treatment, neurological disorders, inflammation, vaccines, and tissue regeneration, highlighting their potential to advance the treatment and management of multiple chronic conditions.Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable and biocompatible copolymer in drug delivery systems (DDSs). This article highlights the critical physicochemical properties of PLGA, including molecular weight, intrinsic viscosity, monomer ratio, blockiness, and end caps, which significantly influence drug release profiles and degradation times. The review covers extensive literature on the application of PLGA in delivering various types of drugs, such as small-molecule drugs, proteins, peptides, antibiotics, and antiviral drugs. PLGA-based DDSs have shown promise in treating various diseases, including cancer, neurological disorders, pain, and inflammation. Incorporating drugs into PLGA nanoparticles and microspheres enhances therapeutic efficacy, reduces toxicity, and improves patient compliance. The article also discusses the latest research on PLGA applications, including innovative formulation techniques and stimuli-responsive formulations. Additionally, it explores the development of PLGA-based delivery systems for combination therapy and hybrid systems that combine PLGA with other polymers or biomaterials. The article provides detailed examples of PLGA-based DDSs in action, such as in pain management, cancer treatment, neurological disorders, inflammation, vaccines, and tissue regeneration, highlighting their potential to advance the treatment and management of multiple chronic conditions.