SPathDB is an extensive database encompassing 1,689,868 manually curated spatial spots from 695 slices across 84 spatial transcriptome datasets of human and mouse tissues. This resource includes data from 36 different tissues and various diseases, such as cancer, and covers 114,998 biological pathways. SPathDB offers interactive tools for the analysis and visualization of functional activities across these spatial spots, facilitating the exploration of pathway-mediated multi-dimensional spatial heterogeneity in the context of functional activity. The database features five versatile tools for data retrieval, analysis, and visualization: Spatial Variable Pathway, Spatial Variable Gene, Spatial Pseudotime, Cell-Cell Communication, and Spatial Deconvolution.