As the Internet of Things (IOT) becomes more widely used in our everyday lives, an increasing number of wireless communication devices are required, meaning that an increasing number of signals are transmitted and received through antennas. Thus, the performance of antennas plays an important role in IOT applications, and increasing the efficiency of antenna design has become a crucial topic. Antenna designers have often optimized antennas by using an EM simulation tool. Although this method is feasible, a great deal of time is often spent on designing the antenna. To improve the efficiency of antenna optimization, this paper proposes a design of experiments (DOE) method for antenna optimization. The antenna length and area in each direction were the experimental parameters, and the response variables were antenna gain and return loss. Response surface methodology was used to obtain optimal parameters for the layout of the antenna. Finally, we utilized antenna simulation software to verify the optimal parameters for antenna optimization, showing how the DOE method can increase the efficiency of antenna optimization. The antenna optimized by DOE was implemented, and its measured results show that the antenna gain and return loss were 2.65 dBi and 11.2 dB, respectively.