A double-blind, placebo-controlled, cross-over trial was undertaken in people with T2D, who were administered 1000mg/day ascorbic acid or placebo for 4-months. Plasma proteins in 26 participants (22 male, 4 female, age 62.6±6.5 years, HbA1c 7.6±0.7%) were quantified by liquid chromatography/mass spectrometry with data independent acquisition. Differential protein expression was assessed for: VC post-supplementation vs. placebo post-supplementation; and VC post-supplementation vs. control [pooling of all non-active conditions]. Pathway enrichments were explored, and correlations between differentially expressed proteins and significantly improved clinical outcomes were assessed.