Nowadays, bio-derived cellulose nano-fibrils based nanocomposites is gaining utmost interest in the area of barrier films for food packaging, as reinforcing filler to make biodegradable nanocomposites with different biopolymers for various applications such as transdermal drug delivery, edible packaging and tissue scaffolding. Ultrasound-assisted preparation of hydroxypropylmethylcellulose based nanocomposites with cellulose nano-fibrils were carried out following solution mixing technique. The crystalline nature of cellulose nano-fibrils has been scrutinized by X-ray diffraction study. The field emission-scanning electron micrographs of cellulose nano-fibrils revealed a network of nano-fibrillar morphology. The Fourier transform infrared spectroscopy results of cellulose nano-fibrils confirmed the removal of lignin and hemicellulose from raw jute (Corchorus olitorius L.) fibres. The storage modulus and tensile properties of hydroxypropyl methylcellulose films increased up to the addition of 1.00 wt% cellulose nano-fibrils. The moisture affinity of hydrophilic hydroxypropylmethylcellulose has also been reduced at 1.00 wt% cellulose nano-fibrils loading. The impact of cellulose nano-fibrils loading on the cumulative percentage of drug release from prepared nanocomposites films has been explored accordingly. By utilizing these versatilities of cellulose nano-fibrils, the fabricated nanocomposites are expected to be highly promising in the area of packaging and transdermal drug delivery system. © 2017 Elsevier B.V.