There is a worldwide increase in the prevalence and incidence of ulcerative colitis (UC) with a lack of adequate treatment for many of these patients. Bilberries (Vaccinium myrtillus or “European blueberries”) possess a naturally high content of anthocyanins (50–80%). Anthocyanins are potential therapeutic agents in gastrointestinal (GI) diseases including UC because of their anti-oxidative and anti-inflammatory properties. An open, prospective, non-blinded, non-controlled pilot trial was conducted for 7 weeks among 13 mild-to-moderate UC patients at the University Hospital Zurich. Inclusion criteria comprised an established diagnosis of mild-to-moderate UC for at least 6-months, an age range between 18 and 65 years old, and a stable use of medication with stable doses for at least 3 months and 4 weeks. During week 1, a full medical history, physical examination, a lab screen, urine analyses and a sigmoidoscopy were obtained. Also, the clinical activity index (CAI) and the complete Mayo Score were determined, the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was completed, and a patient diary was given. Bilberry intake began at week 2 and ended at the week 7 visit. Patients received a daily bilberry dose of 4 trays of 160 g. Remission was 54.5% at the end of 7 weeks. The response rate was 90.9% at end of treatment and 72.7% at end of study. There was a significant reduction in the complete Mayo Score of at least two points in all patients. In 81.8% of patients, the SIBDQ score was significantly higher at end of treatment as compared to screening. Fully blinded examination of biopsy specimen from the rectum and sigmoid colon in random order revealed a decline in acute inflammatory changes, however, these changes did not reach statistical significance (p = 0.17).