Overall, the computational investigation of the natural compounds as PD-L1 inhibitors provides a positive endorsement for the selected natural compounds in the eventual designing and development of an effective small molecule-based anti-PD-L1 agent, which may provide PD-L1 inhibition at low concentration, to disturb the PD-1/PD-L1 signaling pathway for the cancer immunotherapy. The gene discussed is CD274; the disease is cancer.