In this study, the fermentation of Artemisia capillaris by probiotic Leuconostoc mesenteroides MKJW (MKJW) was optimized to increase the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory and antioxidant activities using the response surface method (RSM). The independent variables were the contents of A. capillaris, Gryllus bimaculatus, and yeast extract, while the dependent variables were AChE inhibitory activity, BuChE inhibitory activity, and antioxidant activities such as FRAP, reducing power, and DPPH radical scavenging ability. Seventeen experimental runs were designed with RSM and analyzed after fermentation with MKJW. Quadratic models were used to analyze the inhibition of AChE and BuChE, and a linear model was used to analyze the FRAP. The three models were significantly appropriate (p < 0.0001). The highest optimal condition of the AChE inhibitory activity was derived by a multiple regression equation. When the optimum fermentation conditions were A. capillaris 6.75%, G. bimaculatus 0.18%, and yeast extract 1.27%, 91.1% was reached for AChE inhibitory, 74.0% for BuChE inhibitory, and 34.1 mM FeSO4 for FRAP. The predicted dependent variables were not significantly different from the experimental values (p > 0.05). In conclusion, the A. capillaris fermented by MKJW might be used as a natural antidementia improving agent with AChE inhibitory, BuChE inhibitory, and antioxidant activities.