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As one of the prominent medicinal plants listed in the Chinese pharmacopoeia (2020), Saussurea involucrata (Kar. et Kir.) Sch.-Bip was demonstrated to possess various therapeutic effects. In our recent research, we extracted the polysaccharides from S. involucrata (SIP) at optimal conditions and conducted further structure elucidation on the main fraction as well as the confirmation of its possible anti-inflammatory activity. Hence, in this work, we assessed the in vitro antioxidant activity and anti-melanogenesis effects of the crude SIP in forskolin-induced B16F10 melanoma cells. The results show that SIP possessed strong antioxidant activity and was effective in concentration-dependently decreasing melanin formation and inhibiting tyrosinase activity in forskolin-induced B16F10 cells. Based on these results, the inhibitory mechanism of melanogenesis was investigated by measuring Tyrosinase (TYR), Tyrosinase related protein-1 (TRP-1), Tyrosinase related protein-2 (TRP-2), Microphthalmia-associated transcription factor (MITF), cAMP-response element binding protein (CREB), mitogen-activated protein kinases (MAPK) signaling protein members, and β-catenin degradation in forskolin-induced B16F10 cells. The anti-melanogenesis response of SIP might be attributed to the regulation of c-Jun N-terminal kinase (JNK) phosphorylation and β-catenin degradation pathways. These results suggest that polysaccharides from S. involucrata possess a strong anti-melanogenic effect, and thus could be used as a high-value natural material for skin whitening in cosmeceutical industries.