This study investigates the development of a gypsum-based nanobiocomposite medical plaster reinforced with cellulose extracted from sugarcane bagasse and bioactive compounds derived from rosemary (Rosmarinus officinalis) extract. Rosemary extract was employed for the green synthesis of ZnO nanoparticles, which acted as both reinforcing and antimicrobial agents. Cellulose fibers were extracted from sugarcane bagasse through alkaline treatment followed by hydrogen peroxide bleaching, yielding a lightweight, white, and impurity-free material. Nanobiocomposite samples were prepared by incorporating the ZnO nanoparticles and rosemary extract into medical-grade gypsum, and their mechanical and antimicrobial properties were evaluated. To identify and characterize the synthesis of nanoparticles and investigate their physicochemical properties, tests including UV-Vis, SEM, XRD, and FTIR have been used. Antimicrobial assays demonstrated that green-synthesized ZnO nanoparticles exhibited significant antibacterial activity against Staphylococcus aureus and Escherichia coli, while rosemary extract nanoparticles showed moderate activity against S. aureus only. Impact resistance testing revealed that the addition of nanoparticles increased the absorbed energy of cellulose-reinforced gypsum, with ZnO-containing nanocomposites achieving the highest values at 5 wt.% reinforcement. Overall, the integration of cellulose and rosemary-derived ZnO nanoparticles into gypsum enhances both mechanical strength and antibacterial performance, suggesting potential applications in medical plasters and protective coatings.