Bitter tastes are innately aversive and are thought to help protect animals from consuming poisons. Children are extremely sensitive to drug tastes, and their compliance is especially poor with bitter medicine. Therefore, judging whether a drug is bitter and adopting flavor correction and taste-masking strategies are key to solving the problem of drug compliance in children. Although various machine learning models for bitterness and sweetness prediction have been reported in the literature, no learning model or bitterness database for children’s medication has yet been reported. In this study, we trained four different machine learning models to predict bitterness. The goal of this study was to develop and validate a machine learning model called the “Children’s Bitter Drug Prediction System” (CBDPS) based on Tkinter, which predicts the bitterness of a medicine based on its chemical structure. Users can enter the Simplified Molecular-Input Line-Entry System (SMILES) formula for a single compound or multiple compounds, and CBDPS will predict the bitterness of children’s medicines made from those XGBoost–Molecular ACCess System (XgBoost–MACCS) model yielded an accuracy of 88% under cross-validation.