Abstract Background Most patients with ulcerative colitis (UC) rely predominantly on medication for disease control. Diet interventions can reduce pharmaceutical expenditures and prolong remission. We designed a prospective study to evaluate whether an immunoglobulin G (IgG)-guided exclusion diet would improve symptoms and quality of life (QoL) in patients with UC. Methods The 6-month diet intervention included 97 patients with UC, who were randomly divided into an intervention group (n = 49) and a control (n = 48) group. Individual diet plans were created for the intervention group according to IgG titers; the control group ate a healthy diet as normal. Observational indices included disease activity, extraintestinal manifestations, nutritional status, and QoL. Relationships between food-specific IgG antibodies and these indices were also analyzed. Results At baseline, there were no significant differences between the groups. Food-specific IgG antibodies were detected in 70.10% of participants. After intervention, the Mayo score was significantly lower in the intervention group than in the control group (2.41 ± 0.89 vs 3.52 ± 1.15, P < 0.05). The number of patients with extraintestinal manifestations decreased from 7 to 2 in the intervention group and from 6 to 5 in the control group. As for nutritive indices, the intervention group had higher mean body mass index and albumin than the control group (23.88 ± 3.31 vs 21.50 ± 6.24 kg/m2, respectively, P < 0.05; 48.05 ± 6.39 vs 45.72 ± 5.48 g/L, respectively, P < 0.05), whereas prealbumin and transferrin were not significantly different between the groups. QoL improved after food exclusion (P < 0.05). Conclusions An IgG-guided exclusion diet ameliorated UC symptoms and improved QoL. Interactions between IgG-based food intolerance and UC warrant further study.