In vitro gut microbiome models could provide timely and cost-efficient solutions to study microbiome responses to drugs. For this purpose, in vitro models that maintain the functional and compositional profiles of in vivo gut microbiomes would be extremely valuable. Here, we present a 96-deep well plate-based culturing model (MiPro) that maintains the functional and compositional profiles of individual gut microbiomes, as assessed by metaproteomics, while allowing a four-fold increase in viable bacteria counts. Comparison of taxon-specific functions between pre- and post-culture microbiomes shows a Pearson's correlation coefficient r of 0.83 ± 0.03. In addition, we show a high degree of correlation between gut microbiome responses to metformin in the MiPro model and those in mice fed a high-fat diet. We propose MiPro as an in vitro gut microbiome model for scalable investigation of drug-microbiome interactions such as during high-throughput drug screening.