Aim of the study was to characterize the nutritional composition of 11 apple varieties including 9 varieties from the Regional Repertory of Biodiversity of Marche (Italy). The qualitative and quantitative profiles of polyphenols were evaluated through HPLC-DAD-MS analysis. Antioxidant properties were evaluated by 1,1-diphenyl-2-picrilhydrazyl, ferric reducing antioxidant power, and oxygen radical absorbance capacity assays. The ability of apple extracts to inhibit glyco-oxidative stress was studied using three experimental models: albumin glycated by incubation with fructose or methylglyoxal and human dermal fibroblasts incubated with high-glucose (HG) concentration. The results demonstrated a variability in polyphenolic profile, radical scavenging capacity, and ability to inhibit non-enzymatic glycation of protein.