From the onset of 1940s, antimicrobial agents are widely used to treat a variety of infectious diseases including Urinary Tract Infections, Tuberculosis, Pneumoniae, etc. As a result, overconsumption of broad-spectrum antibiotics has led to an increase in drug resistant strains beside environmental pollution, both of which pose serious threat to the surrounding and human health. Despite their excellent properties, biosensors are not even established as a stable device under some circumstances. Thus, to ensure public health and to minimise antibiotic resistance, nano-biosensors i.e., biosensors with nanomaterial conjugation are being developed for effective eradication of drug residues from the biota. As compared to conventional detection techniques, nano-biosensors are the promising future platforms for easy and quick monitoring of residual drugs in a variety of samples viz., water bodies even at trace element levels. Due to their selectivity, specificity and sensitivity, nano-biosensors are often considered as biocompatible biosensors with integration of nanomaterials having low detection limits and high speed of response. Furthermore, recent developments and modifications for practical applications of nano-biosensors in antibiotic residual detections are suggested to overcome the existing challenges and outlook for future perspectives in this field. Hence, new ideas towards technological advancements will be the key players to prevent antimicrobial resistance and manage public health and hazards for the future generation.