The aim of the study was to develop and evaluate cognitive behavioral therapy for insomnia (CBT-I) among college students with irritable bowel syndrome (IBS). We randomly assigned 60 college students with IBS comorbid insomnia to the experimental group who received CBT-I for 90 min once a week for 4 weeks and the control (non-CBT-I) group. Participants completed self-report measures of insomnia severity, pre-sleep arousal, sleep-related dysfunctional cognitions, maladaptive sleep habits, IBS symptom severity and IBS quality of life (QOL) at baseline, after intervention, and at 3-month follow-up. Sleep pattern, GI symptoms during sleep and Interleukin-6 (IL-6) and C-Reaction Protein (CRP) were measured at baseline and after intervention. The experimental group showed significant decreases in insomnia severity, sleep onset latency, total time in bed, pre-sleep arousal, GI symptoms during sleep, sleep-related dysfunctional cognitions, maladaptive sleep habits, and IBS symptom severity, compared with the control group. This group also showed significant increases in sleep efficiency and IBS QOL compared with the control group. No significant differences were observed between the levels of IL-6 and CRP of both groups. CBT-I for college students with comorbid IBS and insomnia was effective in reducing insomnia, IBS symptom severity, and IBS QOL.