Safflower is an important oilseed crop cultivated primarily for its seeds, which have pharmaceutical properties. Color is an important agronomical trait that appears to be a prior parameter for evaluating the internal quality of plant seeds. This study employs 197 safflower accessions seeds to analyze how their seed coat and flower colors affect their total oil content, fatty acid composition, total phenolic content (TPC), N-(p-coumaroyl)serotonin (CS) and N-feruloylserotonin (FS) contents, and [2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)] radical scavenging activities. Significant variations were observed in the targeted metabolite contents and antioxidant properties among genotypes. Notably, the linoleic acid content, total unsaturated fatty acid content, the ratio of total unsaturated fatty acid to total saturated fatty acid, CS, FS, ABTS, and DPPH scavenging capacities varied significantly based on seed coat color, with white-seeded genotypes having the highest average values of these parameters. Moreover, the linoleic acid content differed significantly (p < 0.05) among the genotypes with varying flower colors, with white-flowered accessions having the highest average content. Furthermore, genotypes K185105 (No. 75) and K175278 (No. 146) were identified as promising genetic resources with health benefits. Overall, these findings reveal that seed coat and flower colors distinctly affect metabolite contents and antioxidant properties in safflower seeds.