MicroRNAs (miRs) play a crucial role in the leukemogenesis and the prognosis of acute myeloid leukemia (AML). This study investigated the therapeutic effects of resveratrol, gallic acid, and piperine as natural anticancer agents on the HL-60 cell line and their roles in apoptosis. In this experimental study, quantitative analysis of miRs, including miR-17, miR-92b, miR-181a, and miR-222, were performed in 150 newly diagnosed patients with AML by real-time PCR assay. HL-60 cell viability as well as the expression of miRs, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA, were also assessed after transfection with the LNA-miRs and treatment with resveratrol, gallic acid, and piperine. The expression of miR-17 and miR-181a decreased significantly in LNA-anti-miRs. Although HL-60 cell viability decreased in LNA-anti-miR-222, miR-17, and miR-92b, blockade of miR-181a increased the cell viability. Besides, the cell viability increased merely in the piperine-treated group. Compared to untreated cells, miR-17 and miR-92b expression significantly increased in gallic acid- and resveratrol-treated cells. In HL-60 cells treated with resveratrol, gallic acid, and piperine, the expression of miR-181a was also increased significantly. The expression of BAX was also increased in resveratrol and piperine-treated groups. Compared to untreated cells, the expression of c-Kit increased significantly in the piperine-treated group; however, it decreased in the resveratrol-treated group. LNA-anti-miRs may be a promising agent for the treatment of AML. All three compounds used in this study showed anticancer effects, which can exert the desired outcome in patients with AML.