A new series of 21 Schiff bases of spiro-isatin was synthesized, and their DPPH, CUPRAC and ABTS cation radical scavenging abilities were investigated for antioxidant activity. The results showed that all the synthesized compounds exhibited antioxidant activity for each assay. 5 & x30d;-(2,3-Dihydroxybenzylideneamino)spiro[[1,3] dioxolane-2,3 & x30d;-indoline]-2 & x30d;-on (5c) (IC50 = 4.49 mu M, for DPPH; IC50 = 0.39 mu M, for ABTS(.+); and A(0.50) = 0.42 mu M, for CUPRAC) showed significantly better ABTS, CUPRAC and DPPH radical scavenging ability than quercetin (IC50 = 8.69 mu M, for DPPH; IC50 = 15.49 mu M, for ABTS(.+); and A(0.50) = 18.47 mu M, for CUPRAC), which is used as a standard. SAR study showed that the synthesized compounds had higher ABTS(.+) activity than DPPH and CUPRAC activities. Moreover, the compounds (5c and 5d), containing two hydroxyl groups, exhibited the highest antioxidant activities for all assays. Quantum chemical calculations were also carried out to support SAR results.