Three major sources of flavonoids and phenolic compounds, which are commonly used in food industry, namely loquat leaf (LL), grape skin (GS) and acai puree, were tested in regard to their potential anti-atherosclerotic and anti-diabetic activity. The compounds were evaluated by in vitro antioxidant assay using a macrophage model and for in vivo hypolipidemic activity using zebrafish. In assays in vitro, all extracts demonstrated potent ferric ion reductive capacity, radical-scavenging activity and inhibition of low-density lipoprotein (LDL) oxidation at a final concentration of 0.1 mg/ml. Extracts could also abrogate fructose-mediated protein glycation and mildly inhibit cholesteryl ester transfer protein (CETP). Cellular uptake of oxidized or acetylated LDL into macrophages was inhibited by acai treatment (final concentration, 0.1 mg/ml) and moderately diminished by GS and LL extracts. After 4 weeks of feeding on a high cholesterol diet (HCD), zebrafish exhibited serum total cholesterol (TC) and triglyceride (TG) levels 2.5-fold higher than those fed a normal diet (ND). Within the experimental group, those fed acai demonstrated the lowest serum TC and CETP activity, while the LL-consuming group showed a reduction in serum TC and TG relative to HCD-fed fish. Serum glucose levels also increased in the HCD group, to threefold above the ND group; GS and LL feeding elicited the greatest reduction in hyperglycemia. The groups consuming acai and LL showed much less hepatic inflammation, as well as attenuation of fatty liver and a reduced content of oxidized species. In conclusion, extracts of LL, GS, and acai shared antioxidant, anti-inflammatory and anti-atherosclerotic activity in cellular assays and in a hypercholesterolemic zebrafish model.