Multiplex fiber-optic biosensor implemented by integrating multiple particle plasmon resonances (PPRs), molecular bioassays, and microfluidics is successfully demonstrated. The multiple PPRs are achieved by chemical immobilization of silver nanoparticles (AgNPs) and gold nanorods (AuNRs) separately on two unclad portions of an optical fiber. The difference in morphology and nature of material of AgNPs and AuNRs are exploited to yield multiple plasmonic absorptions at 405 and 780 nm in the absorption spectrum measured from optical fiber by white light source illumination. Through the coaxial excitation of light-emitting diodes (LEDs) with 405 and 800 nm wavelengths, the distinct PPRs are advantageous for real-time and simultaneous detection of multiple analyte-probe pairs as AgNPs and AuNRs are separately functionalized with specific bio-probes. Here, the multi-window fiber-optic particle plasmon resonance (FO-PPR) biosensor has been shown to be capable of simultaneously detecting anti-dinitrophenyl antibody (anti-DNP, MW = 220 kDa) via N-(2,4-dinitrophenyl)-6-aminohexanoic acid (DNP, MW = 297.27 Da) functionalized AgNPs and streptavidin (MW = 75 kDa) via N-(3-aminopropyl) biotinamide trifluoroacetate (biotin, MW = 414.44 Da) functionalized AuNRs. The multiplex sensing chip possesses several advantages, including rapid and parallel detection of multiple analytes on a single chip, minimized sample to sample variation, reduced amount of sensor chip, and reduced analyte volume, hence it is ideally suitable for high-throughput multiplex biochemical sensing applications.