The study integrated peripheral blood RNA single-cell sequencing (GSE125527) and bulk sequencing (GSE75214) data from patients with ulcerative colitis (UC) and Crohn's disease (CD) to identify molecular differences. The analysis revealed in UC patients IL-17A+ effector memory T cells and enriched leukocyte migration pathways, while in CD the processes of immune cell activation IL-1β and B-production dominated. Cross integration identified 43 consistently dysregulated genes and 10 hub genes (THBS1, PLAUR, KLF4, CD36, CD44, CXCR4, FOS, S100A9, ANXA1, TIMP1). An 18-gene machine learning model achieved an AUC of 0.73 in independent validation (GSE179285). The potent biomarkers LDHB, MGAT4A and PSME2 have had limited previous reports in UC/CD classification. Immunohistochemical validation confirmed subtype-specific expression: GZMA and PSME2 increased in CD, LDHB and FOSB in UC. The approach revealed differences in immune regulation, metabolism and tissue remodeling.