Aim: To assess the suppressive effects of glabridin (GLA) on colorectal cancer (CRC) cells. Methods: After treating cultured CRC cell lines in vitro with different concentrations of GLA, cell proliferation was examined through cell counting kit-8 (CCK-8) and 5-ethynyl-2 '-deoxyuridine (EdU) assays, and cell migration and invasion were determined by Transwell migration and invasion assays. Quantitative polymerase chain reaction (qPCR) and Western blotting were carried out to detect expression levels of intercellular adhesion molecule 1 (ICAM1) mRNA (messenger ribonucleic acid) and phosphorylated (p)-signal transducer and activator of transcription 3 (STAT3) protein. ICAM1-associated downstream pathways were analyzed via the LinkedOmics database. Results: GLA inhibited proliferation, migration, and invasion of SW620 and HT-29 cells. Additionally, ICAM1 was found as a downstream target of GLA, and GLA suppressed the expression levels of ICAM1 and p-STAT3. ICAM1 overexpression reversed the effects of GLA on CRC cell multiplication, migration, invasion, and p-STAT3 protein expression. Conclusions: GLA restrains the malignant phenotypes of CRC cells via regulating ICAM1/p-STAT3 signaling pathway.