Upon pathogen attack, plants activate their immune response as a defense mechanism. AP2/ERF transcription factors are known to regulate these immune responses. Halostachys caspica belonging to Amaranthaceae, an exceptionally salt-tolerant halophyte, is widely distributed in the arid and saline-alkali regions of Xinjiang, in Northwest China. In our study, we explored the effects of HcmiR172e and its target gene, the AP2 subfamily transcription factor HcTOE3 from H. caspica, on the plant’s reaction to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) and Verticillium dahliae (VD991). We found that HcTOE3 is responsive to both Pst DC3000 and VD991, as well as to hormone treatments, including salicylic acid (SA), methyl jasmonate (MeJA), ethylene (ET), and 6-benzylaminopurine (6-BA). HcTOE3 transgenic Arabidopsis plants showed enhanced resistance to Pst DC3000 and VD991 infections compared to control plants. This resistance was associated with increased reactive oxygen species (ROS) accumulation, improved photosynthetic efficiency, reduced stomatal aperture, and increased lignin content in roots. Additionally, HcTOE3 significantly upregulated the expression of key genes involved in SA and JA signaling pathways, such as AtPR1, AtPR2, AtPR5, AtPDF1.2, and AtVSP2, as well as defense marker genes AtWRKY53, AtERF104, and AtPAD4. In contrast, HcmiR172e transgenic Arabidopsis plants exhibited an opposing trend in these indicators. Further, yeast one-hybrid and dual-luciferase assays confirmed that HcTOE3 can bind to the promoters of downstream defense-related genes, including AtPR1, AtPDF1.2, AtPR2, and AtVSP2, through possible cis-acting elements, such as TTTGTT, AGCTA, GAAG, and MYB motifs. Altogether, our findings indicate that HcTOE3 positively modulates Arabidopsis resistance against Pst DC3000 and VD991, while HcmiR172e negatively regulates Arabidopsis’s involvement in plant immune defense responses. This research offers new insights and evidence for further exploration of the role of AP2 subfamily members in the mechanisms of biotic stress resistance.