Chenopodium quinoa Willd. is rich in phenolic compounds and exhibits diverse biological activities. Few studies have focused on the effect of colored quinoa’s phenolic profile on potential biological activity. This study used a UPLC–MS/MS-based metabolomic approach to examine the quinoa phenolics and their association with in vitro antioxidant and hypoglycemic properties. In total, 430 polyphenols, mainly phenolic acids, flavonoids, and flavonols, were identified. Additionally, 121, 116, and 148 differential polyphenols were found between the white and black, white and red, and black and red comparison groups, respectively; 67 polyphenols were screened as shared key differential metabolites. Phenylalanine, tyrosine, and the biosynthesis of plant secondary metabolites were the main differently regulated pathways. Black quinoa had better total phenolic contents (643.68 mg/100 g DW) and antioxidant capacity, while white quinoa had better total flavonoid contents (90.95 mg/100 g DW) and in vitro α-amylase (IC50 value of 3.97 mg/mL) and α-glucosidase (IC50 value of 1.08 mg/mL) inhibition activities. Thirty-six polyphenols, including epicatechin and linarin, etc., were highly correlated with in vitro antioxidant activity, while six polyphenols, including tiliroside and chrysoeriol, etc., were highly correlated with in vitro hypoglycemic activity. This study may provide important information for colored quinoa resources to develop their healthy food applications.