Ulcerative colitis is a bowel disease of unknown cause. This research is a proof-of-concept exercise focused on determining whether it is possible to identify the genes associated with ulcerative colitis using artificial intelligence. Several machine learning and artificial neural networks analyze using an autoimmune discovery transcriptomic panel of 755 genes to predict and model ulcerative colitis versus healthy donors. The dataset GSE38713 of 43 cases from the Hospital Clinic of Barcelona was selected, and 16 models were used, including C5, logistic regression, Bayesian network, discriminant analysis, KNN algorithm, LSVM, random trees, SVM, Tree-AS, XGBoost linear, XGBoost tree, CHAID, Quest, C&R tree, random forest, and neural network. Conventional analysis, including volcano plot and gene set enrichment analysis (GSEA), were also performed. As a result, ulcerative colitis was successfully predicted with several machine learning techniques and artificial neural networks (multilayer perceptron), with an overall accuracy of 95–100%, and relevant pathogenic genes were highlighted. One of them, programmed cell death 1 ligand 1 (PD-L1, CD274, PDCD1LG1, B7-H1) was validated in a series from the Tokai University Hospital by immunohistochemistry. In conclusion, artificial intelligence analysis of transcriptomic data of ulcerative colitis is a feasible analytical strategy.