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Background Rice varieties enriched with potential bioactive compounds are poised to make a significant contribution to global health. It is anticipated that edible medications made from rice seeds will lead to novel therapeutics.Purpose High-yielding popular pigmented and nonpigmented rice varieties were selected for in-depth analysis of bioactive contents. Nutraceutical potential of high-yielding rice varieties often goes underexplored compared to low-yielding specialty rice varieties. This study addresses the gap by metabolomic profiling of popular rice varieties to uncover bioactive compounds with significant pharmaceutical and nutritional benefits.Methods Untargeted metabolomic profiling of the brown rice of pigmented and nonpigmented varieties was conducted by Orbitrap-high-resolution liquid chromatography and mass spectrometry, and primary and secondary metabolites were identified and annotated. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging (RS) assay was carried out to identify the variety with superior antioxidant activity. Correlation analysis by using Metaboanalyst software identified major metabolites with RS potential. Over-representation analysis was performed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and major pathways were identified for metabolites with nutraceutical potential in pigmented rice.Results Major metabolites with antioxidant, anti-inflammatory, and anticarcinogenic properties were identified from rice varieties. Bioactive compounds detected from brown rice included choline, didodecyl-3,3-thiodipropionate, conjugated linoleic acid, oleic acid, 13(S)-HOTrE, monoolein, nicotinic acid, pantothenic acid, isoquinoline, trigonelline, corymboside, ferulic acid, and 2,4-quinolinediol. The DPPH RS assay revealed superior antioxidant activity in the pigmented rice, with differential metabolites from the pathways of phenylpropanoid biosynthesis, arginine and proline metabolism, and biosynthesis of unsaturated fatty acids showing a significant correlation (p< .01) with RS potential.Conclusion Catechin, (–)-epicatechin, (±)12(13)-DiHOME, 4-guanidinobutyric acid, and 5-methoxysalicylic acid are key metabolites that emphasize the antioxidant potential of red-colored rice as a functional food with significant health benefits. The study highlights the therapeutic promise of pigmented whole-grain rice.