Regional ecological safety is of great significance in coordinating the relationship between land use and ecological environment, promoting the rational allocation of resources and achieving the coordinated regional development. Taking the Lanzhou-Xining urban agglomeration (LXUA) as a typical area, this paper applies Morphological Spatial Pattern Analysis (MPSA) to study the optimal configuration of land use functions, and provides new ideas for regional layout optimization by constructing the MSPA-GMOP-PLUS coupling model to incorporate ecological security into the optimization of land use functions and spatial structure of urban agglomerations. The results show that:(1) the ecological source areas are of great significance to regional ecological security, and there were 20 ecological source areas in the LXUA in 2020, with an ecological core area of 43,355.5 km². In addition, the ecological protection zone still accounts for the largest area (30.7%) in the functional land use zoning, and the ecological fringe area also accounts for 19.2%, providing a buffer zone for the ecological protection. (2) The new simulation model can limit the unbalanced development trend of urban agglomerations and is superior to the traditional land use planning model. The proportion of productive, living and ecological land under the new model is optimized from 30.17%, 11.25% and 55.58% in the traditional model to 31.92%, 10.70% and 57.38%, respectively. The optimization results not only ensure the stability of quality production space, but also effectively ensure the sustainability of ecological space. In addition, the results of the land use layout under different development scenarios can be used as a reference for improving land resource utilization and formulating spatial land use planning.