Cucumber mosaic virus (CMV), one of the main viruses, is responsible for Passiflora spp. (passion fruit) virus diseases, which negatively affect its planting, cultivation, and commercial quality. In this study, a laboratory anti-CMV activity screening model for Passiflora spp. CMV disease was first established. Then, the effects of different antiviral agents of chitosan oligosaccharide (COS), dufulin (DFL), and ningnanmycin (Ning) on CMV virulence rate in Passiflora spp. were determined. The virulence rate and anti-CMV activity in Passiflora spp. treated with COS were 50% and 45.48%, respectively, which were even better than those of DFL (66.67% and 27.30%, respectively) and Ning (83.30% and 9.17%, respectively). Field trials test results showed COS revealed better average control efficiency (47.35%) against Passiflora spp. CMV disease than those of DFL (40.93%) and Ning (33.82%), indicating that COS is effective in the control of the Passiflora spp. CMV disease. Meanwhile, the nutritional quality test results showed that COS could increase the contents of soluble solids, titratable acids, vitamin C, and soluble proteins in Passiflora spp. fruits as well as enhance the polyphenol oxidase (PPO), superoxide dismutase (SOD), and peroxidase (POD) activity in the leaves of Passiflora spp. seedlings. In addition, the combined transcriptome and proteome analysis results showed that COS mainly acted on the Brassinosteroids (BRs) cell signaling pathway, one of plant hormone signal transduction pathway, in Passiflora spp., thus activating the up-regulated expression of TCH4 and CYCD3 genes to improve the resistance to CMV disease. Therefore, our study results demonstrated that COS could be used as a potential plant immune inducer to control the Passiflora spp. CMV disease in the future.