Nanoformulation-based controlled-release systems (CRS) have significantly advanced drug delivery by enabling sustained, targeted, controlled therapeutic release, reducing side effects, and enhancing patient compliance. Natural polymers, such as alginate, chitosan, gelatin, and guar gum, have gained prominence due to their biocompatibility, biodegradability, and eco-friendly properties, making them superior alternatives to synthetic polymers. These polymers are extensively used across oral, parenteral, and transdermal drug delivery systems, providing site-specific and stimuli-responsive drug release based on pH, temperature, or enzymatic activity. Advances in nanotechnology, including polymeric nanoparticles, hydrogels, and microspheres, have further improved drug stability, bioavailability, and targeting efficiency. Additionally, sustainable production methods, such as microbial fermentation and enzymatic polymerization, have addressed scalability challenges, ensuring the commercial viability of natural polymer-based CRS. Regulatory bodies have increasingly recognized biodegradable polymeric carriers, streamlining their approval and accelerating their integration into modern therapeutics. As research progresses, the focus will shift toward hybrid natural-synthetic systems, computational modeling for optimizing drug release kinetics, and bioengineered polymers for personalized medicine. With continuous innovations, natural polymer-based CRS will play a crucial role in the future of pharmaceutical formulations, offering safer, more effective, and patient-centric drug delivery solutions.