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Background Acute radiation proctitis (ARP) is a common complication of radiation therapy (RT). This adverse effect in severe cases ultimately results in interruption of RT and poor outcome. Aloe vera contains multiple antioxidant and anti-inflammatory compounds This study was aimed to evaluate the preventive effects of Aloe vera in ARP in colorectal cancer.Method: twenty eligible colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% ointment or placebo for six weeks. At each weekly visit, ARP symptoms were evaluated by Radiation Therapy Oncology Group (RTOG) and clinical presentation criteria. The lifestyle impact of the symptoms, depression and anxiety for assessment of psychosocial status of patients, and quantitative CRP were evaluated as secondary endpoints.Results there was a significant improvement in the symptom index for diarrhea and total RTOG scores and quantitative CRP levels (between-subject differences or group effect) (p Aloe group. The overall time trend (within-subject differences or time effect) was statistically significant for rectal bleeding, rectal pain, total clinical scores, proctitis, cystitis, and total RTOG (P Aloe vera group. The median lifestyle score improved significantly with Aloe vera. Intervention patients had a lower probability of presenting anxiety in their overall HAD scale during RT.Conclusion The use of topical formulation of Aloe vera 3% diminished the severity of ARP in colorectal cancer patients. Trial registration: Current Controlled Trials IRCT201606042027N6, registrations date: 2016-04-09.