Water and glucose, as two essential species involved in physiological processes, play indispensable roles in maintaining body fluid homeostasis and energy metabolism. Therefore, investigating their mutual-diffusion process is of great significance for understanding physiological processes and developing related technologies. Here, a fiber-integrated plasmonic microsensor, with high space-time resolution and high refractive index (RI) sensitivity, is proposed for in situ monitoring the water-glucose diffusion process and determining the diffusion coefficient. The sensor is a spiral-grating tapered gold tip integrated on the end face of an optical fiber. Benefiting from its compact size of ~14×10×10 μm
3 and high RI sensitivity of ~258.19 nm/RIU, it enables high-precision detection of glucose concentration in microscopic regions. Therefore, the spatial distribution of glucose concentration in the liquid can be obtained by scanning this sensor and measuring the concentration point by point. By repeatedly scanning this microsensor in diffusing liquids, the glucose concentration space-time evolution for the diffusion processes between water and glucose solutions at concentrations of 20% and 15% has been measured, in a time range of 1 h, and a space range of ~15 mm with a space resolution of ~15.3 μm. The experimental results show that the diffusion processes follow Fick’s law, and the corresponding diffusion coefficients are determined to be 6.33×10
-10 m
2/s and 6.83×10
-10 m
2/s, respectively, based on the Fickian diffusion model. The results confirm that the diffusion coefficient is smaller for the diffusion system with higher glucose concentration, consistent with existing literature. This method can be used for monitoring the diffusion process with large space-time range, high spatial resolution, and easy operation performance, thereby providing an effective and high-performance scheme for investigating liquid diffusion.