Based on the LC-MS/MS molecular networking strategy, nine undescribed 2-isobutylmalate derivatives, namely bletistrosides M-U (compounds 1-7, 9, and 11), together with two known analogues (compounds 8 and 10), were isolated and identified from the leaves of Bletilla striata. Their structures with absolute configurations were deduced from spectroscopic data, acidic hydrolysis, and comparison with reported compounds. Compounds 1/2, 3/4, 5/6, and 7/8 represented four pairs of Z/E isomers regarding cinnamoyl groups, and each pair underwent interconversion under UV radiation at 254 nm. Biologically, compounds 1, 2, and 10 exhibited anti-pulmonary fibrosis effects against bleomycin-stimulated cell injury in A549 cells. Further investigations demonstrated that the anti-pulmonary fibrosis potential of 2 was related to the inhibition of apoptosis and epithelial-mesenchymal transition by blocking the Bax/Bcl-2, TGF-beta 1/Smad2/3, and PI3K/AKT signaling pathways, while concurrently enhancing the Nrf2 signaling pathway.