Background: Chronic rhinosinusitis is a prevalent and complex disease associated with symptoms that interfere with patients’ quality of life. Although there are many treatment options, they are linked with sideeffects and high patients’ dissatisfaction. Little studies were conducted to test the effect of Nigella sativa (N. sativa) on chronic rhinosinusitis which is known for its beneficial effects on inflammation. Therefore, the aim of this trial is to examine the effect of N. sativa nasal oil drops on symptoms severity and treatment satisfaction among patients with chronic rhinosinusitis. Methods: This trial was performed as a prospective, open-labelled and comparative clinical trial design on 102 patients with chronic rhinosinusitis. Patients were randomly assigned to either the control group which used the standard medical treatment only or the study group that received N. sativa nasal oil drops in addition to the standard medical treatment for four consecutive weeks. Outcomes were assessed five times; once every two weeks for eight consecutive weeks using Sino-nasal Outcomes Test-22 and Treatment Satisfaction Questionnaire for Medications, where the total scores were compared between both groups using two independent samples t-test. Results: Initial assessment showed no significant differences between both groups in the mean total scores of severity of symptoms and patient satisfaction. But, during and post-intervention assessments revealed significant differences between the two groups (p≤ .005) except satisfaction with side-effects. These differences sustained at the follow-up period as measured at the first and the second follow-up postintervention assessments. The main trial’s primary outcomes were nasal obstruction/congestion, postnasal discharge and facial pain/pressure, where the relative risks (RR) were 0.70, 0.48 and 0.42 respectively, whereas, the secondary outcomes were fatigue, reduced productivity, reduced concentration, frustration/restlessness/irritability, sadness and patient dissatisfaction. Conclusion: Nigella sativa nasal oil drops had a significant positive effect on severity of symptoms of chronic rhinosinusitis and patients’ satisfaction, hence, it is recommended to be integrated with the standard medical treatment for those patients. Also further trials are recommended to support the positive effect of Nigella sativa on chronic rhinosinusitis. Trial Registration no: NCT05494164 (Registration date 9/8/2022 https://clinicaltrials.gov/study/NCT05494164).