The rise of antibiotic resistance presents a critical challenge in healthcare, necessitating the development of novel antimicrobial strategies. Simultaneously, the sustainable management of agricultural waste, such as oil palm fronds (OPFs), is essential for mitigating environmental pollution. This study focuses on the production and characterisation of cellulose nanocrystals (CNCs) derived from oil palm frond fibres (OPFF) and their potential as carriers for antibiotics. The fibres were pretreated with bleaching and alkaline processes, followed by CNC extraction via weak acid and enzymatic hydrolysis. Fourier Transform Infrared Spectroscopy confirmed the removal of hemicellulose and lignin during alkaline treatment, while thermogravimetric analysis demonstrated enhanced thermal stability. Antimicrobial assays revealed that CNC alone exhibited no activity and CNC-erythromycin (ERY) displayed limited efficacy. In contrast, CNCtetracycline hydrochloride (TAC) demonstrated significant antibacterial activity against Pseudomonas aeruginosa (Gram-negative), while showing no improvement against Staphylococcus aureus (Grampositive). These findings highlight the selective antimicrobial enhancement of CNC-antibiotic formulations, demonstrating the potential of CNC derived from OPFF as a functional material for targeted antibiotic delivery while addressing both biomedical challenges and environmental sustainability.