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We investigated the angiogenesis‐modulating ability of noscapine in vitro using osteosarcoma cell line (MG‐63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG‐63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real‐time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG‐63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG‐63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl2) induced hypoxic signaling molecules' gene expression in MG‐63 cells and zebrafish embryos. Therefore, noscapine may prevent MG‐63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions. [ABSTRACT FROM AUTHOR]