Lignocellulosic biomass is widely grown in many agricultural-based countries. These are typically incinerated or discarded in open spaces, which further may cause severe health and environmental problems. Hence, the proper utilization and conversion of different parts of lignocellulosic biomasses (e.g., corn wastes derived leave, cob, stalk, and husk) into value-added materials could be a promising way of protecting both health and environments. In addition, they have high-potential for myriads applications (e.g., pharmaceuticals, cosmetics, textiles, and so on). In this context, herein, we isolated holocellulose (a mixture of alpha α, beta β, and gamma γ cellulose) from corn waste, and then it was converted into carboxymethyl cellulose (CMC). Subsequently, the prepared CMC was evaluated successfully to be used as a pharmaceutical excipient. Different characterization tools were employed for structural, morphological, and thermal properties of the extracted holocellulose and synthesized CMC. Results showed that the highest yield of CMC was obtained 187.5% along with the highest degree of substitution (DS i.e., 1.83) in a single stage (i.e., size reduction technique) with the lowest particle size of holocellulose (100 µm). This happened due to the use of a single stage instead of multiple stages. Finally, extracted CMC was successfully used as a pharmaceutical excipient with promising results compared to commercially available pharmaceutical-grade CMC.