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Abstract This study explores the utilization of eight readily available agricultural waste varieties in Nigeria—sugarcane bagasse, corn husk, corn cob, wheat husk, melina, acacia, mahogany, and ironwood sawdust—as potential sources of cellulose. Gravimetric analysis was employed to assess the cellulose content of these wastes, following which two selected wastes were combined based on their cellulose content and abundance to serve as the raw material for the extraction process. Response Surface Methodology, including Box-Behnken design, was applied to enhance control over variables, establish an optimal starting point, and determine the most favorable reaction conditions. The cellulose extracted under various conditions was comprehensively examined for content, structure, extent of crystallinity, and morphological properties. Characterization techniques such as X-ray Diffraction, Scanning Electron Microscopy, and Fourier Transform Infrared Spectroscopy were employed for detailed analysis. Compositional analysis revealed sugarcane bagasse and corn cob to possess the highest cellulose content, at 41 ± 0.41% and 40 ± 0.32% respectively, with FTIR analysis confirming relatively low C=C bond intensity in these samples. RSM optimization indicated a potential 46% isolated yield from a hybrid composition of sugarcane bagasse and corn cob at NaOH concentration of 2%, temperature of 45 °C, and 10 ml of 38% H2O2. However, FTIR analyses revealed the persistence of non-cellulosic materials in this sample. Further analysis demonstrated that cellulose isolated at NaOH concentration of 10%, temperature of 70 °C, and 20 ml of 38% H2O2 was of high purity, with a yield of 42%. Numerical optimization within this extraction condition range predicted a yield of 45.6% at NaOH concentration of 5%, temperature of 45 °C, and 20 ml of 38% H2O2. Model validation confirmed an actual yield of 43.9% at this condition, aligning closely with the predicted value. These findings underscore the significant potential of combinning and utilizing agricultural wastes as a valuable source of cellulose, paving the way for sustainable and resource-efficient practices in various industrial applications.