The objective of this work is to re-use of agriculture waste via an environmentally friendly procedure to introduce multifunctional cellulose-based blend films using sesame seed meal extracted from agriculture wastes. The current strategy demonstrated the identification and evaluation of the bioactive compounds of sesame seed meal extracted from agricultural wastes via an ultrasonic procedure. Then, the sesame seed meal extract was loaded onto modified carboxymethyl cellulose within a matrix of a blend film. A cross-linked blend films based on the biocompatible modified carboxymethyl cellulose (m-CMC) with phenolic compounds (Ph) extracted from sesame seed meal were developed. The cross-linked m-CMC/Ph films were investigated by Fourier transform infrared spectroscopic analysis, while the surface morphology was investigated using scanning electron microscopy. Both mechanical and swelling properties were investigated. The m-CMC/Ph film exhibited excellent antioxidant performance as well as antibacterial activity against Staphylococcus aureus as Gram-positive pathogenic bacteria and Pseudomonas aeruginosa as Gram-negative pathogenic bacteria using colony-forming unit to provide further biocompatibility for prepared blend films. Additionally, molecular docking studies were carried out on effective films to evaluate their potential interaction against P. aeruginosa LolA (PDB: 2W7Q) and S. aureus metalloproteinase (PDB:1BQB) with a binding energy of - 3.7 kcal/mol and - 2.8 kcal/mol and short bond length of 2.076 angstrom and 1.144 angstrom, respectively. The computational calculations of the optimized monomer CMC and gallic acid were carried out to elucidate the HOMO-LUMO energy gap and interaction between them as well as the optimization of m-CMC/Ph to evaluate their interaction and film stability. As a result, the present study presents a novel simple approach to design smart biocompatible films for multifunctional healthcare and medical purposes using the biologically active extracts from sustainable plant wastes.