Fabrication and experimental validation of a newly developed copper oxide nanoparticles (CuO-NPs) and silver nanoparticles (AgNPs) immobilized SM-MM-SM-MM-SM (SMSMS) in-line Mach-Zehnder interferometer (MZI) fiber structure-based sensor using localized surface plasmon resonance (LSPR) technique are reported in this article. The AgNPs and CuO-NPs are used to improve the biocompatibility and sensitivity of the sensor. The nanoparticles (NPs) and immobilized probe were characterized by UV-Vis spectrophotometer, HR-TEM, SEM, and EDX, revealing superior performance over the existing uric acid (UA) sensors. The proposed optimized structure-based optical fiber sensors (OFSs) exhibit excellent specificity, sensitivity, and limit of detection (LoD) for the detection of UA. Moreover, the developed sensor exhibits linear profile over a very wide range: 1) 10 μM-1 mM for detection over UA presents in serum, while the normal range of UA in serum is 100-400 μM and 2) 0.4-10 mM for detection over UA presents in urine, while the normal range of UA in urine is 1.5-4.4 mM. In addition, the developed sensor has a distinguished advantage, such as multicompatibility over the detection of UA presents in both serum and urine along with its high selectivity, reusability, reproducibility, and lowest LoD. The proposed AgNPs and CuO-NPs immobilized and the uricase functionalized SMSMS structure-based LSPR sensor has better compatibility and are potent candidates for medical applications.