As a new resource food, Moringa oleifera leaves has attracted much attention for its hypoglycemic activity, however, the active components need further study. The chemical fingerprint can distinguish the difference of chemical content in medicinal materials, and the spectrum-effect correlation analysis can preliminarily predict the active component groups. The insulin resistance model of HepG2 was used to evaluate the hypoglycemic activity of Moringa oleifera leaves, and the main active components with hypoglycemic activity in Moringa oleifera leaves were identified by the spectrum-effect correlation analysis with fingerprint. This paper evaluated the hypoglycemic activity of different extracts from orthogonal test and found that Moringa oleifera leaves could increase the glucose consumption of insulin resistant HepG2 cells and effectively alleviate insulin resistance. Spectrum-effect correlation analysis indicated that apigenin-7-O-glucoside, quercetin-3-O-glucoside, kaempferol diacetyl-rhamnoside, kaempferol had higher correlation coefficient and they were 0.991 (P < 0.01), 0.915 (P < 0.01), 0.988 (P < 0.01), 0.987 (P < 0.01), respectively. The results of this study provided the basis for the discovery of hypoglycemic active component group of Moringa Oleifera leaves. The hypoglycemic active component group of Moringa Oleifera leaves might be apigenin-7-O-glucoside, quercetin-3-O-glucoside, kaempferol diacetyl-rhamnoside, kaempferol.