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Photonic crystal fiber (PCF)-based biosensors have emerged as highly efficient optical sensing devices because of their superior light confinement capability, structural flexibility, and tunable optical characteristics. This review presents a comprehensive overview of recent developments in PCF-assisted biosensors integrated with surface plasmon resonance (SPR) technology for biomedical applications. The influence of structural parameters such as pitch spacing, air-hole diameter, and plasmonic coating thickness on resonance conditions and sensing performance is critically analyzed. These biosensors have demonstrated remarkable capability in detecting glucose, serum proteins, pathogens, pH levels, cancerous cells, and biochemical analytes in blood, urine, saliva, food, water, and environmental samples. The paper discusses the operating principles, structural classifications, and sensing mechanisms of PCF biosensors while comparing their performance with conventional optical sensing systems. Different PCF configurations including dual-core, hollow-core, D-shaped, rectangular-core, octagonal-core, and hexagonal structures are reviewed based on sensitivity, confinement loss, and refractive index detection range. The findings indicate that SPR-assisted PCF biosensors possess strong potential for future biomedical diagnostics, environmental monitoring, and intelligent healthcare systems because of their compact size, enhanced sensitivity, and fabrication flexibility.