Abstract: A method and device for drug combination design by a high-throughput platform and machine learning for optimizing is provided, including: constructing an initial data set for machine learning using the high-throughput platform; inputting the initial data set into a plurality of machine learning models, and training the plurality of regression models; predicting unknown D-amino acid mixtures using the machine learning models and an efficient global optimization algorithm; and conducting experimental iterative feedback on a candidate mixture formula, and conducting high-throughput performance screening on drug combinations of D-amino acid mixtures and a plurality of antibiotics optimized by machine learning. The performance screened is the drug resistance of bacteria to antibiotics, and antibacterial efficiency and cytotoxicity of the drug combinations.