Gastric cancer (GC) is considered the 3rd most lethal cancer among cancer, followed by lung and colorectal cancer. The GC cases are increasing gradually, with an escalation rate of 5.7% approximately documented only in 2019. According to the record of 2015, the majority of the new cases, nearly 50% of patients were diagnosed in South and Central America, Eastern Europe, and East Asia. In comparison, North America, Africa, South Asia, Australia, and New Zealand found significantly fewer cases. Mushrooms have a long history to be used as a medicine and food source, believed a delicious and healthy food source. Lentinula edodes, also known as shiitake mushrooms, have the potential for anti-tumor activity. Recent studies showed Lentinula edodes have potential and significant effects on cell apoptosis and its well-intentioned source to decrease the antagonistic reactions of chemotherapy. Peptides acquired from Lentinula edodes (LP-1, LP-13) provided substantial results on various cancer types, increasing apoptosis. LP-1 is also reported to inhibit migration, and invasion of GC cells by arresting cell growth at the S phase via the phosphatidylinositol-3-kinase (PI3K)/Akt pathways.