This study aimed at evaluating the effect of high-energy milling (HEM) and traditional nixtamalization (TN) on bioactive compounds and antioxidant capacity in nixtamalized creole corn flours obtained from a maize genotype cultivated under rainy temporal conditions in the Mexican semidesert. Four creole grains, including San José de Gracia white and blue (WG and BG), Negritas (NG), and Ahualulco white corn grains (SG), were used. For HEM nixtamalization, corn grains were hammer-milled; then, two different conditions were evaluated: treatment H1, with raw flours with 14% moisture content and 1.1% Ca(OH)2, and treatment H2, with raw corn flours with a 23% moisture content and 1.4% Ca(OH)2. The TN process was utilized as a control. TN recorded significant losses in luminosity value L* (p < 0.05), while HEM nixtamalized blue corn flours remained close to -b* values, that is, near to those of raw flour. Anthocyanin content showed higher content values in HEM treatments compared with TN (759.55 and 252.53 mg cyanidin 3-O-β-D-glucoside (C3G)/kg, respectively) (p < 0.05). Total soluble phenolic content was higher in HEM nixtamalization compared with the traditional process, except for WH2 and SH2 (H2 treatment for WG and SG). Two redundant radical scavenging assays were used: antioxidant capacity (DPPH assay) exhibited less value in nixtamalized flours than in raw flour (p < 0.05). Antioxidant activity by (ABTS) assay was higher in HEM than in TN. Nixtamalized flours produced by HEM demonstrated more improvement in nutraceutical properties than those produced employing TN.