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Plant root-knot nematode disease is a great agricultural problem and commercially available nematicides have the disadvantages of high toxicity and limited usage; thus, it is urgent to develop new nematicides derived from nature substances. In this study, a novel fluorinated derivative was synthesized by modifying chitosan oligosaccharide (COS) using the strategy of multiple functions. The derivatives were characterized by FTIR, NMR, elemental analysis, and TG/DTG. The activity assays show that the derivatives can effectively kill the second instar larvae of <i>Meloidogyne incognita</i> in vitro, among them, chitosan-thiadiazole-trifluorobutene (COSSZFB) perform high eggs hatching inhibitory activity. The derivatives can regulate plant growth (photosynthetic pigment), improve immunity (chitinase and β-1,3-glucanase), and show low cytotoxicity and phytotoxicity. According to the multi-functional activity, the derivatives exhibit a good control effect on plant root-knot nematode disease <i>in vivo</i>. The results demonstrate that the COS derivatives (especially fluorinated derivative) perform multiple activities and show the potential to be further evaluated as nematicides.