A facile and ultrasound assisted green methodology was adopted to achieve spirooxindolo-1,2,4-oxadiazoles via a [3+2] cycloaddition of aryl nitrile oxides and isatin Schiff bases at room temperature with good yields and lesser reaction times. The proposed procedure avoids traditional column chromatography resulting in good to excellent yields. The synthesized compounds were evaluated for their anti-cancer activity against SK-OV-3, HeLa, HCT-116, DU-145, A549 and HEK-293 cell lines. Two of them showed significant anti-cancer activity against HeLa with IC50 value 10.75±0.39 µM and 12.43±0.77 µM respectively. In vitro anti-cancer activity X-ray structure Molecular docking Good yields up to 85% Less reaction time Column chromatography free