Objective: To explore the targets and signaling pathways of Radix Pseudostellariae-Rhizoma Anemarrhenae treating diabetes mellitus by network pharmacology and expound its mechanism. Methods: The TCMSP and SymMap databases were used to screen out the active ingredients and targets of Radix Pseudostellariae-Rhizoma Anemarrhenae. The GenCards database was used to screen the predicted targets of diabetes mellitus. Two targets were mapped. The Cytoscape 3.7.2 software was used to construct the network diagram of Chinese medicine-active ingredient-target and screen out the core ingredient and target. The GO,KEGG pathway enrichment analysis was carried out by OmicShare and David. Results: According to the screening criteria, 23 active ingredients of Radix Pseudostellariae-Rhizoma Anemarrhenae and 146 potential targets were obtained. 138 common targets were obtained related with diabetes mellitus, including 5 key components and 37 core targets. The enrichment of biological process in GO is mainly related to the reaction to organic substances, the response of cells to chemical stimulation, the reaction to chemical substances, etc.. The molecular function is mainly related to the enzyme binding, the same protein binding, and the activity of nuclear receptor. The cell composition is mainly associated with the membrane raft, membrane microdomain, membrane region, etc.. The KEGG pathway enrichment is mainly concentrated in TNF, Toll-like receptors, NOD-like receptors, insulin resistance and type Ⅱ diabetes. Conclusion: Radix Pseudostellariae-Anemarrhena asphodeloides plays the anti-inflammatory, antioxidant, hypoglycemic, and insulin-resistance improving role through multiple targets and pathways, and therefore achieves the effect on diabetes mellitus.