Mechanochemistry was applied to improve the yield of bioactive acid polysaccharides obtained from low-cost Senecio scandens Buch.-Ham. The structural characteristics and biological activities of three novel polysaccharides from S. scandens (SP2-1, SP2-2 and SP3-2) were investigated. SP2-1 and SP2-2 with molecular weights of 267.6 and 253.1 kDa, respectively, were composed of L-rhamnose, D-arabinose, D-mannose, D-xylose, D-glucose and D-galactose in various ratios, whereas SP3-2 with molecular weight of 266.6 kDa was composed of D-arabinose, D-glucose and D-galactose. In vitro, SP3-2 presented the strongest DPPH, ABTS and O2− radicals scavenging activities, as well as Fe3+ reducibility. Immunological tests demonstrated that all polysaccharide fractions stimulated the production of nitric oxide (NO) and immunomodulatory cytokines (IL-1β and TNF-α) without cytotoxicity in macrophages and promoted splenocyte proliferation in different degree. These findings indicated that SP2-1, SP2-2 and SP3-2 have prominent antioxidant activity and potential immune response, which proved the possibility of S. scandens polysaccharides (SSP) applied in the field of functional food or medicine.