Ulcerative colitis is a pathological condition characterized by recurrent colon inflammation, causing symptoms such as diarrhea, nausea and abdominal discomfort. In vitro, studies have demonstrated that Lactoferrin directly impacts intestinal immunity and reduces inflammation by altering the production of inflammatory cytokines in immune cells. Plantago ovata's seed husk, known as Psyllium, are frequently taken as a dietary supplement to help with digestive problems. The study investigated the induction of the colitis model in rats using a 1ml of acetic acid (4%) enema inserted into the rectum. Oral Lactoferrin with a dose of (30 mg/animal/day) and Psyllium seed husk colloid with a dose of (15 mg/animal/day) for 7 days were used as treatments. Animals were divided into seven groups with different treatments. Rats' stool was examined and scored. Serum C- reactive protein (CRP), Interleukin-10, and Interleukin-17 were estimated with some oxidative stress parameters evaluated in colon tissue homogenate. Immunohistochemical Interleukin-6 and histological examinations of the colon were assessed. The study found that oral administration of lactoferrin and/or Psyllium significantly improved the severity of colon inflammation by reduction in colon wet-to-dry ratio, colon inflammatory index, serum Interleukin-17, protein expression of Interleukin-6 and CRP, Colon homogenate malondialdehyde (MDA) and myeloperoxidase (MPO) activity. Also, increased serum Interleukin-10 and Glutathione (GSH) levels were determined. The inflamed colons treated with Lactoferrin and/or Psyllium showed a mostly normal histopathological examination with minimal erosion. The present study revealed that Lactoferrin and/or Psyllium prospered to decrease levels of colonic and systemic inflammation in rats-induced colitis, hopefully postponing disease progression.