<p>Natural polymers such as chitosan, alginate, starch, cellulose, guar hum, gelatin, carrageenan, and xanthan gum have emerged as versatile biomaterials owing to their biocompatibility, biodegradability and derivation from renewable resources. Despite such advantages, unmodified or non-grafted forms suffer limitations, including poor mechanical strength, rapid dissolution, and uncontrolled water retention, restricting their usage in drug delivery and biomedical applications. Grafting synthetic polymer side chains onto natural backbones enhances solubility, stability, improves drug release and imparts stimuli-responsive behavior. A variety of grafting methods, including free radical polymerization, enzymatic catalyst, click chemistry, radiation and plasma induced methods and microwave-assisted approaches, enable precise structural modification with contrasting efficiency and scalability. Successful grafting is confirmed by employing various characterizing techniques and are discussed in the review. Further, applications in drug delivery include oral systems with improved mucoadhesion and sustained drug release, transdermal films and hydrogels with enhanced permeation, colon-targeted formulations using pH-OR enzyme responsiveness, bio-adhesive ocular and nasal systems, and nano-carriers such as micelles for hydrophobic drugs. Apart from drug delivery, biomedical applications span tissue engineering scaffolds, antimicrobial wound dressings, gene and protein delivery systems, biosensors, and functionalized implants with reduced immune responses. While limitations remain in reproducibility, scalability and regulatory approval, advances in green chemistry and stimuli-responsive grafting promise next-generation “smart” biomaterials. Collectively, grafted natural polymers represent a rapidly advancing toolkit for drug delivery and biomedical applications, bridging the gap between natural biopolymers and engineered therapeutic platforms.</p>