Red wine is rich in anthocyanins and procyanidins which possess multiple health-promoting properties. However, the synergistically anticancer effects of them on gastric cancer cells still undefined. The results showed that combination of malvidin-3-O-(6-O-coumaroyl)-glucoside-5-O-glucoside (M35GC) and procyanidin C1 could effectively inhibited the viability of MKN-28 cells with the lowest IC50 value. Mechanistically, M35GC and procyanidin C1 significantly induced cell apoptosis by reducing the ratio of Bcl-2/Bax, blocked cell cycle in G0/G1 phase by decreasing CDK4 protein and decreased glucose consumption and lactate production during aerobic glycolysis through suppressing the expression of HK2 protein in MKN-28 cells. In conclusion, induction of cell apoptosis and cell cycle arrest, as well as the inhibition of HK2 protein that participates in the glycolytic pathway and the suppression of aerobic glycolysis by M35GC and procyanidin C1 contributed to the anti-cancer effects in gastric cancer.