This study aimed to investigate the effects of the Mediterranean diet (MD), combined with curcumin and resveratrol supplementation, on disease activity, serum inflammatory markers, and quality of life in patients with mild-to-moderate active ulcerative colitis (UC). This study was designed as a prospective multicenter three-arm randomized controlled trial. Participants were randomized to the MD, MD + curcumin, and MD + resveratrol groups. All participants were placed on the MD for 8 weeks. The MD + curcumin group also received 1600 mg/day of curcumin supplementation, whereas the MD + resveratrol group received 500 mg/day of resveratrol supplementation for 8 weeks. Anthropometric measurements, Truelove–Witts Index, Short Form-36, Inflammatory Bowel Disease Questionnaire, Mediterranean Diet Adherence Scale (MEDAS), and laboratory tests were performed at baseline and postintervention. Within-group comparisons showed that MD, MD + curcumin, and MD + resveratrol interventions were effective in reducing disease activity and inflammation and improving quality of life in individuals with UC (p < 0.05). Between-group comparisons revealed no significant difference in all parameters except for the pain subparameter of SF-36 and the MEDAS score (p < 0.05). The MD is an effective and safe intervention to be used in clinical practice in individuals with UC.