This study aimed to analyze the therapeutic effect of nanomedicine on bronchial asthma and the effect of vitamin 1,25-(OH)2D3 on airway remodeling. The four groups of Z1 (1,25-(OH)2D3+RNPEG-ABT-199), Z2 (RNPEG-ABT-199), Z3 (ABT-199), and Z4 (normal Control) were designed in this study. The prepared acid-responsive mitochondrial targeting nanomedicine (RNPEG-ABT-199) and non-responsive mitochondrial targeting nanomedicine (PEG-ABT-199) were applied to the treatment of asthma mouse models. The results showed the PU value of caspase-3 in Z4 was lower than Z1, Z2, and Z3 groups; and in Z3 was higher than Z1 and Z2 groups. IL-4, IL-5, and TNF-α levels in Z3 were obviously higher than Z1, Z2, and Z4 groups, while those in the Z1 were obviously lower than the Z2 and Z4 groups; the proliferation activity of airway smooth muscle cells (ASMCs) of Z3 was obviously higher than the Z1, Z2, and Z4 groups, and that of the Z1 was obviously lower than the Z2 group. In short, RNPEG-ABT-199 has stronger lysosomal escape ability and mitochondrial targeting than PEG-ABT-199. RNPEG-ABT-199 can cause apoptosis of inflammatory cells and decrease pro-inflammatory cytokines, which is better than PEG-ABT-199. Vitamin1,25-(OH)2D3 can obviously inhibit the proliferation activity of ASMCs cells, and be used in the treatment of asthma along with RNPEG-ABT-199.