Uveal melanoma is the most common form of eye cancer and has a poor prognosis. Although the primary tumor in most cases is treated effectively by local surgery or radiotherapy, over 50 % of patients develop systemic metastasis, especially in the liver. In contrast to cutaneous melanoma, there is no standard-of-care treatment for metastasized uveal melanoma. Recently, oncogenic driver mutations in GNAQ or GNA11 were identified in about 85 % of uveal melanomas, which lead to constitutively active signaling in the Gα pathway and its downstream effectors. Direct targeting of deregulated Gα signaling might therefore be a therapeutic option for patients with uveal melanoma. In our study we identified the cyclic depsipeptide FR-900359, which is isolated from the evergreen plant Ardisia crenata as an effective inhibitor of constitutively active Gα proteins and their downstream targets. Although our data are preliminary, they might contribute to a future treatment option for patients with metastasized uveal melanoma.