Designing a suitable, cost-effective nanocarrier with an ability to capture and deliver antibiotics for restricting microbial spread remains an unmet need. A simple two-stepped strategy involving citric acid-induced hydrolysis of cellulose pulp (NFC) followed by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) mediated oxidation to obtain carboxylated nano fibrillated cellulose (TNFC-5) with high carboxyl content (1.12 mmol/g) has been explored. TNFC-5 so obtained was able to capture remarkable extent of antibiotics (drug loading (DL) > 40 % and entrapment efficiency (EE) >80 %) irrespective of their hydrophilicity as in, triclosan (hydrophobic) and ampicillin sodium (hydrophilic). In silico molecular docking study revealed the excess carboxyl content in nanocellulose imparted the strongest binding affinity to antibiotics via H-bonding. A slower and sustained release of triclosan was observed for TNFC-5 than that of NFC, reiterating the enhanced binding efficiency of the drugs with TNFC-5. Well-dispersed triclosan loaded TNFC-5 displayed sustained antibacterial activity against Escherichia coli and Staphylococcus aureus up to one week. Thus, TNFC-5 has been demonstrated as a green, cheap, and eco-friendly alternative to the other biodegradable nanocarriers for carrying antibiotics with high DL and EE, thereby reducing the wastage of expensive drugs while ensuring a sustained antibacterial effect. Our study established that the drug loaded nanofibers (TNFC-5) might act as a promising candidate to penetrate through biofilm for treating serious bacterial infections by retarding their growth and eventually eradicating bacterial colonies.