Gastro-retentive drug delivery systems (GRDDS) are designed to enhance the bioavailability and therapeutic efficacy of drugs by prolonging their residence time in the stomach. These systems offer significant advantages for drugs with narrow absorption windows or those that require a controlled release profile to optimize their therapeutic action. Recent advancements in GRDDS have focused on improving the design and functionality of these systems to address challenges such as variability in gastric emptying times, stomach pH fluctuations, and drug degradation in the acidic environment of the stomach. Key innovations include floating systems, mucoadhesive systems, bioadhesive polymers, and expandable systems, each with its own advantages and limitations. In addition, newer techniques, such as the use of stimuli-responsive materials and nanotechnology, have shown promise in achieving more precise and efficient drug delivery. This review discusses the latest advances in the development of GRDDS, with a focus on novel materials, technologies, and the clinical implications of these systems.