Pharmacology experts place a high priority on therapeutic plants because the majority of pharmaceutical firms rely on medicinal plants as raw ingredients. Therefore, the potential bioactive components using gas chromatography–mass spectrometry analysis and antioxidant effects using DPPH free radical scavenging activity of various crude fractions of Xanthium spinosum were assessed. Gas chromatography–mass spectrometry analysis showed the presence of various bioactive compounds including benzenedicarboxylic acid (18.60%), 8‐octadecenoic acid (4.86%), 11‐octadecenoic acid and 10‐octadecenoic acid in the crude methanolic extract, 1,2‐benzenedicarboxylic acid, diisooctyl ester (14.42%), 1,2‐benzenedicarboxylic acid, mono (2‐ethylhexyl) ester (14.42%), 6‐octadecenoic acid, methyl ester (7.56%), 8‐octadecenoic acid, methyl ester (7.56%), 10‐octadecenoic acid, methyl ester (7.56%) and hexadecanoic acid, methyl ester (6.55%) in the n‐hexane extract, ethanal, 2‐methyl‐2‐[4‐(1‐methylethyl)phenyl]‐(3.02%), (+)‐3‐carene, 4‐isopropenyl‐(3.02%), 7H‐indeno[5,6‐b] furan‐7‐one, 4,4a,5,6,7a,8‐hexahydro‐ (3.02%) and 2‐[5‐(2,2‐dimethyl‐6‐methylene‐cyclohexyl)‐3‐methyl‐pent‐2‐enyl]‐[1,4] benzoquinone (2.79%) in the chloroform extract and 1,2‐benzenedicarboxylic acid, mono (2‐ethylhexyl) ester (33.005%), 1,2‐benzenedicarboxylic acid, diisooctyl ester (33.005%) and bis(2‐ethylhexyl) phthalate (33.005%) in the ethyl acetate extract. Significant DPPH radical scavenging activity was exhibited by the chloroform fraction (43.37–88.65%) at all doses followed by the crude methanolic extract (36.02–83.75%) at all doses. In conclusion, different crude fractions of X. spinosum can be considered a rich source of pharmacologically active components that can be scoped for isolation and may be subjected to in‐depth pharmacological study.