Due to highly personalized biological and lifestyle characteristics, different individuals may have different metabolic responses to specific foods and nutrients. In particular, the gut microbiota, a collection of trillions of microorganisms living in our gastrointestinal tract, is highly personalized and plays a key role in our metabolic responses to foods and nutrients. Accurately predicting metabolic responses to dietary interventions based on individuals’ gut microbial compositions holds great promise for precision nutrition. Existing prediction methods are typically limited to traditional machine learning models. Deep learning methods dedicated to such tasks are still lacking. Here we develop a new method McMLP (Metabolic response predictor using coupled Multilayer Perceptrons) to fill in this gap. We provide clear evidence that McMLP outperforms existing methods on both synthetic data generated by the microbial consumer-resource model and real data obtained from six dietary intervention studies. Furthermore, we perform sensitivity analysis of McMLP to infer the tripartite food-microbe-metabolite interactions, which are then validated using the ground-truth (or literature evidence) for synthetic (or real) data, respectively. The presented tool has the potential to inform the design of microbiota-based personalized dietary strategies to achieve precision nutrition.