Seaweeds are important source of bioactive compounds, including sulfated polysaccharides (SP). Because of their structural heterogeneity, these compounds are promising sources of anticancer compounds. SP from brown and red seaweeds have shown antimelanoma activity in different in vitro and in vivo models. However, SP from green seaweed are still poorly evaluated. Therefore, SP were extracted from the green alga Caulerpa cupressoides var. flabellata, and their antiproliferative, anti-migratory, and inhibitory effect on melanin production on B16-F10 melanoma cells was evaluated. Cell assays, including flow cytometry, demonstrated that SP (100–1000 μg mL−1) are non-cytotoxic, do not induce apoptosis or necrosis, and do not interfere with cell cycle. However, SP (1000 μg mL−1) were found to significantly inhibit cell colony formation (80–90%), cell migration (40–75%), and melanin production (~ 20%). In summary, these results showed that SP inhibited important melanoma development events without cytotoxicity effects, suggesting that C. cupressoides may be an important source of SP with antitumor properties.