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In recent decades, glaciers in the southeastern Tibetan Plateau (SETP) have been rapidly melting and showing a large scale of glacier mass loss. Due to the lack of large-scale, high-resolution, and high-precision observations, knowledge on the spatial distribution of the glacier mass balance and the response to climate change is limited in this region. We propose a TanDEM-X bi-static InSAR (Interferometric Synthetic Aperture Radar) algorithm with a non-local mean filter method and difference strategy, to improve the precision of glacier surface elevation change detection. Moreover, we improved the glacier mass balance estimation algorithm with a correction method for multi-source system errors and an uncertainty evaluation method based on error propagation theory to reduce the uncertainty of estimations. We used 13 pairs of TanDEM-X bi-static InSAR images to obtain the glacier mass balance data for the entire SETP. The total area of glaciers monitored was 5821 km2 and the total number of glaciers monitored was 2321; the glacier surface elevation change rate was −0.505 ± 0.005 m/yr, and the glacier mass balance estimation was −454.5 ± 13.1 mm w.eq. during 2000–2014. Additionally, we analyzed the spatial distribution of the glacier mass balance within the SETP using the sub-watershed analysis method. The results showed that the mass loss rate had a decreasing trend from the southeast to the northwest. Furthermore, the temperature change and the glacier mass loss rate showed a positive correlation from the southeast to the northwest in this region. This study greatly advances our understanding of the regularities of glacier dynamics in this region, and can provide scientific support for major national goals such as the rational utilization of surrounding water resources and construction of important transportation projects. [ABSTRACT FROM AUTHOR]