It is important to monitor refractive index (RI) and temperature (T) simultaneously for photo-thermal therapy (PTT) in the blood circulation system. However, the fluctuation of T sways the RI response owing to high cross-sensitivity. To address the issue, a fiber-optic-based localized surface plasmon resonance (LSPR) sensor with a cascaded structure of a single-mode fiber-multimode fiber-single-mode fiber (SMF-MMF-SMF) is presented for synchronous measurement of RI and T. This detection principle is founded on the synergistic effects of the Mach-Zehnder interference (MZI) and LSPR. The cascaded structure was fabricated to inspire MZI, while LSPR was excited by gold nanoparticles/polydopamine (AuNPs/PDA) deposited on the fiber surface. The MZI and LSPR spectra were extracted and reconstructed using spectrum transformation and filtering techniques to sort the original spectra. The sensor achieved simultaneous detection of RI and T with a sensitivity of 3.58 (a.u.)/RIU and -0.0011 (a.u.)/°C, respectively. Additionally, the MZI signals near the LSPR wavelength in the absorption spectra are used to replace the extracted LSPR signal. Compared with the LSPR signal, the MZI signal exhibited over 30 times enhancement on the figure of merit (FOM) value due to its narrow full width at half maxima (FWHM). The sensor provided a novel strategy for synchronous measurement of RI and T, making it a promising alternative for