Activation of the innate immune system before the invasion of pathogens is a promising way to improve the resistance of plant against infection while reducing the use of agricultural chemicals. Although several elicitors were used to induce the resistance of potato plant to microbial pathogen infection, the role of curdlan oligosaccharide (CurdO) has not been established. In the current study, the defense responses were investigated at biochemical and proteomic levels to elucidate the elicitation effect of CurdOs in foliar tissues of potato (Solanum tuberosum L. cv. McCain G1). The results indicate that the CurdOs exhibit activation effect on the early- and late-defense responses in potato leaves. In addition, glucopentaose was proved to be the shortest active curdlan molecule based on the accumulation of H₂O₂ and salicylic acid and the activities of phenylalanine amino-lyase, β-1,3-glucanase and chitinase. The 2D-PAGE analysis reveals that CurdOs activate the integrated response reactions in potato cells, as a number of proteins with various functions are up-regulated including disease/defense, metabolism, transcription, and cell structure. The pathogenesis assay shows that the ratio of lesion area of potato leaf decreased from 15.82%±5.44% to 7.79%±3.03% when the plants were treated with CurdOs 1 day before the infection of Phytophthora infestans. Furthermore, the results on potato yield and induction reactions indicate that the defense responses induced by CurdOs lasted for short period of time but disappeared gradually.