<p>Curcumin, a polyphenolic small molecule extracted from turmeric, possesses anti-inflammatory, anti-cancer, and wound-healing effects. Structural models of cellulose nanofibers in cylindrical and planar configurations were employed to examine curcumin attachment, surface distribution, and stability via molecular docking and molecular dynamics (MD) simulations. Curcumin was preferentially attached to the ends of cylindrical arrangements while being more uniformly distributed across the surface of planar configurations. This uniform distribution seems to be facilitated by forming additional hydrogen bonds, suggesting enhanced stability in interaction with planar arrangements. MD simulations revealed that curcumin establishes a more stable interaction with planar nanofibers, whereas, in its interaction with cylindrical arrangements, it functions as an adhesive, holding the fibers together. The results suggest that cylindrical configurations of cellulose nanofibers provide faster delivery of curcumin, and the planar support more stable as well as extended administration. The implications of the computational results were further examined through experimental approaches. Scanning electron microscopy results indicated that the presence of curcumin would alter the diameter of cellulose nanofibers loaded with curcumin compared to cellulose nanofibers alone. Fourier Transform Infrared Spectroscopy confirmed changes in surface functional groups, validating the successful loading of curcumin. UV spectra further supported the integration of curcumin into the nanofiber structure. These findings demonstrate that cellulose nanofibers provide a stable platform for curcumin distribution, enhancing molecular interactions. Our study employed molecular docking, MD simulations, and experimental validations to present the potential use of cellulose nanofibers in developing effective targeted drug loading, release, and delivery systems, particularly for sustained and localized treatments.</p>