To reduce the limit of detection (LOD) in fiber optic localized surface plasmon resonance (FO LSPR) sensors, design strategies with high scattering efficiency and low background signal are proposed. Despite the cost effectiveness of fabrication, miniaturization capabilities, and high portability of optic fibers, the LOD is a limiting factor for fiber optic sensor applications. To overcome this limitation, we propose methods to increase the scattering efficiency and reduce background signal using gold capping and reactive-ion etching (RIE). Specifically, three strategies are implemented. First, the effective coverage for detection is selected by analyzing the sensor output according to the density of gold nanoparticles (AuNPs), which have been immobilized on the cross-section of the optical fiber. Next, the sensitivity is studied by examining changes in scattering efficiency of the AuNPs grown with different capping times. Third, RIE is performed on the fiber optic surface to reduce the reflectance in areas where the AuNPs are not fixed, thereby decreasing the background signal. Thyroglobulin, amyloid beta monomer, and oligomer are measured using the thus-fabricated FO LSPR sensor. The results are compared with those obtained with a sensor fabricated without using these strategies. The former showed the lower LOD and higher accuracy for biomarkers of the two. • The effective coverage of AuNPs is selected on the optical fiber. • For improvement of scattering efficiency, AuNPs are directly grown on fiber optic surface. • Surface etching is executed for reduction of background in bare surface. • The enhancement of the LODs is evaluated for several biomarkers.