Ulcerative colitis is a systemic inflammatory disease which primarily involves the gut but presented by numerous extraintestinal manifestations. The effect of ulcerative colitis on knee cartilage has not been evaluated up to the present. In the current study, we aimed to investigate the possible relationship between the presence of ulcerative colitis and femoral cartilage thickness. Sixty-two patients with confirmed diagnosis of ulcerative colitis and 70 healthy controls aged 18 to 50 years referred to the gastroenterology outpatient department between January 2018 and January 2019 participated in this cross-sectional study. The measurements were made by ultrasonography with the patient in a supine position and the knees in complete flexion. Demographic, clinical, endoscopic and laboratory data were collected for all the subjects. The groups of ulcerative colitis and control group were similar with regard to sex, mean age, weight, height, body mass index, extremity dominancy, and existence of knee pain (P > 0.05). Medial femoral condyles, intercondylar areas, and lateral femoral condyles of both right and left knees had thinner cartilage thickness in ulcerative colitis group than control group (P < 0.001). Knee cartilage was thinner in subjects with mild activity ulcerative colitis than in healthy controls. Decreased knee cartilage thickness may be an indicator of extraintestinal manifestation in patients with mild activity ulcerative colitis. This association between ulcerative colitis and knee cartilage degeneration may be effective in early detection of possible risk factors and potential treatment strategies for both ulcerative colitis and specific subtypes of knee osteoarthritis.