Gynostemma pentaphyllum (Thunb.) Makino was traditionally used as antiatherogenic foods in China but ingredients responsible for the effects remained unexplored. Here, kaempferol 3-O-[2G-(E)-Coumaroyl-3G-O-beta-D-glucosyl-3R-O-beta-D-glucosylrutinoside] (KCGG), gypenoside XLVI (GPXLVI), gypenoside LI (GPLI), gypenoside L (GPL), ginsenoside Rd (GSRd) and 2 alpha, 3 beta, 12 beta, 20 (S)-tetrahydroxy-25-hydroperoxy-dammar-23-ene-20-O-beta-D-glucopyranosyl-(1 -> 6)-beta-D-glucopyranoside (GLUP) were isolated, among which KCGG, GPLI and GLUP exhibited greater antioxidant potential. The predominant inhibitory effects of KCGG, GPLI and GLUP on oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and intracellular lipid accumulation were further confirmed at non-cytotoxic concentrations. KCGG mainly decreased interleukin-6 (IL-6) production, while GPLI and GLUP were more powerful in inhibiting interleukin-1 beta (IL-1 beta) accumulation. KCGG, GPLI and GLUP significantly inhibited extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation. They also dramatically promoted cholesterol efflux through up-regulating scavenger receptor class B type I (SRB1) expression. In conclusion, KCGG, GPLI and GLUP acted through different pathways that acted simultaneously.