This review comprehensively explores the synthesis, properties, sustained release mechanisms, and applications of poly(lactic-co-glycolic acid) (PLGA) hydrogels in drug delivery. PLGA hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and versatile properties. The review highlights various synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, each with its advantages and disadvantages. Sustained release mechanisms such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems are analyzed, along with key kinetic models for designing controlled drug delivery systems. Applications of PLGA hydrogels in localized and sustained chemotherapy for cancer, as well as in delivering antibiotics and antimicrobials, are discussed. Challenges and future prospects in PLGA hydrogel research are also addressed, focusing on improving drug loading efficiency, release control mechanisms, and clinical translation. The review emphasizes the potential of PLGA hydrogels to revolutionize therapeutic delivery and improve patient outcomes.This review comprehensively explores the synthesis, properties, sustained release mechanisms, and applications of poly(lactic-co-glycolic acid) (PLGA) hydrogels in drug delivery. PLGA hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and versatile properties. The review highlights various synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, each with its advantages and disadvantages. Sustained release mechanisms such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems are analyzed, along with key kinetic models for designing controlled drug delivery systems. Applications of PLGA hydrogels in localized and sustained chemotherapy for cancer, as well as in delivering antibiotics and antimicrobials, are discussed. Challenges and future prospects in PLGA hydrogel research are also addressed, focusing on improving drug loading efficiency, release control mechanisms, and clinical translation. The review emphasizes the potential of PLGA hydrogels to revolutionize therapeutic delivery and improve patient outcomes.