The main objective of the present work was to study the optimization of microwave drying of potatoes that have different flesh colors. The effects of independent variables of microwave power (300, 450, 600 W), slice thickness (2–4, 6 mm), and steam blanching time (2, 5, 8 min) on the color, total phenolic content (TPC), antioxidant activity, starch ratio, and total monomeric anthocyanin content (TMA) were investigated by using the Response Surface Methodology (RSM). Before drying, potato slices that had different thicknesses were blanched in steam at 90 °C for indicated times. Optimization was applied to improve bioactive compounds, starch ratio, and color. The optimum drying parameters were determined as 300 W, 6 mm, and 8 min for purple-fleshed potatoes, and 450 W, 6 mm, and 2 min for yellow-fleshed potatoes. This study is beneficial to the development of the processing of potatoes in the food industry and provides more insights into the application of microwave drying technology.