Liquid biopsies have emerged as a key tool that enables personalized medicine, enabling precise detection of biochemical parameters to tailor treatments to individual needs. Modern biosensors enable real-time detection, precise diagnosis, and dynamic monitoring by rapidly analyzing biomarkers such as nucleic acids, proteins, and metabolites in bodily fluids like blood, saliva, and urine. Despite their potential, many biosensors are still constrained by mono-functionality, sub-optimal sensitivity, bulky designs, and complex operation requirements. Recent advances in stimuli-responsive smart materials present a promising pathway to overcome these limitations. These materials enhance biomarker signal transduction, release, or amplification, leading to improved sensitivity, simplified workflows, and multi-target detection capabilities. Further exploration of the integration of these smart materials into biosensing is therefore essential. To this end, this review critically examines and compares recent progress in the development and application of physical, chemical, and biochemical stimuli-responsive smart materials in biosensing. Emphasis is placed on their responsiveness mechanisms, operational principles, and their role in advancing biosensor performance for biomarker detection in bodily fluids. Additionally, future perspectives and challenges in developing versatile, accurate, and user-friendly biosensors for point-of-care and clinical applications using these smart materials are discussed.