The study examined the effect of natural compounds found in Artemisia douglasiana and Artemisia tridentata extracts on survival and melanogenesis of B10F16 metastatic murine cells. The cells were exposed to short UVB and IBMX treatments to determine their ability to regulate melanogenesis. IBMX-treated cells showed a more robust effect on the production of melanin. B10F16 cells were treated with Artemisia tridentata and DhL, an active natural compound extracted from Artemisia douglasiana, showed a clear inhibitory effect in IBMX-stimulated cells. Tyrosinase activity was observed in supernatants after DhL and Artemisia tridentata extracts were added. Artemisia tridentata showed the strongest inhibitory effect on melanogenesis in vitro and utilized the tyrosinase pathway to prevent melanin production in B10F16 cells. Artemisia douglasiana showed an inhibitory effect of melanogenesis in vitro but it appears to use a different pathway to inhibit melanogenesis. Therefore, it is important to continue studying Artemisia tridentata and Artemisia douglasiana for their inhibitory properties on melanogenesis.