Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such as extraction solvent, extraction time, and extraction temperature, were optimized using response surface methodology. Regression analysis showed a good fit of this model and yielded the second-order polynomial regression for tyrosinase inhibition and antioxidant activity. Among the extraction variables, extraction solvent greatly affected the activity. The optimal condition was determined as EtOAc concentration in MeOH, 69.6%; temperature, 10.0 °C; and extraction time, 24.2 h, and the tyrosinase inhibitory and antioxidant activity under optimal condition were found to be 57.9% and 49.3%, respectively. Further analysis showed the close correlation between activities and phenolic content, which suggested phenolic compounds are active constituents of bee pollen for tyrosinase inhibition and antioxidant activity. Taken together, these results provide useful information about bee pollen as cosmetic therapeutics to reduce oxidative stress and hyperpigmentation.