Sandwich assay employing gold nanoparticles and DNA is a common signal amplification strategy designed for surface plasmon resonance sensor. To further improve the sensitivity employing sandwich assay, sandwich-structured optical fiber surface plasmon resonance sensors based on AuNPs and MoS2 nanosheets has been theoretically studied. Au film deposited on fiber core is the bottom nanomaterial of sandwich structure while AuNPs and MoS2 nanosheets are optional used as top nanomaterials. Top and bottom nanomaterials are separated by double stranded DNA, which allows solvent to perform as a spacer. The thickness of spacer is able to be tuned by the number of base pairs of double stranded DNA. Spacer thickness and nanomaterials play important roles to regulate the performance of optical fiber surface plasmon resonance sensor. The refractive index sensitivity has been found to be enhanced by the presence of MoS2 nanosheets compared to AuNPs. Large spacer thickness supported by long double stranded DNA further improves the performance of sensor. This study yields new insight into the structural design of optical fiber surface plasmon resonance sensor enhanced by sandwich structure and will open exciting avenues to apply sandwich-like assay for biosensing.