Tau protein extensively phosphorylated at threonine 217 (p-tau217), has emerged with significant potential for initial clinical identification of Alzheimer’s disease (AD). In this study, a simple but sensitive electrochemiluminescence (ECL) immunosensor was designed for p-tau217 detection based on antigen–antibody specific binding to modulate the spatial hindrance of the gold electrode interface. Silica nanoparticles doped with ruthenium bipyridine (Ru@SiO2 NPs) were used as the ECL indicator. The p-tau217 monoclonal antibody was initially fixed onto the gold electrode surface, selectively capturing the p-tau217 protein, which subsequently increased the steric hindrance of the electrode. This process allowed for a decreased amount of Ru@SiO2 to access the electrode surface, which resulted in the relatively low ECL intensity being detected. The variation in ECL intensity exhibited a strong linear correlation with the logarithm of the target concentration, spanning from 1 pg/mL to 100 ng/mL, and a detection limit of 0.178 pg/mL was achieved. The proposed approach was effectively implemented to detect target in the serum of AD patients, and it delivered satisfactory outcomes.