Background: Hyaluronic acid (HA) and berberine hydrochloride are thought to be effective postoperative factors after chronic rhinosinusitis (CRS) nasal surgery.Objective: This study aimed to assess the effects of berberine hydrochloride with or without adding hyaluronic acid in adult patients of chronic rhinosinusitis, with or without polyps, who were scheduled for bilateral endoscopic sinus surgery. Patients and methods: The patients were randomly assigned into two groups based on the way of postoperative intervention used. Thus, gel foam with berberine was used for the first group (B group), and berberine with hyaluronic acid was used for the second group (HB group). In every case, this aforementioned procedure was done in one nasal cavity of the nose with a focus on the middle meatus, but saline only was used with gel foam in the other cavity, after surgery, respectively. During the postoperative visits on 5, 10, 30, and 90,180 days, the patients were asked to complete a questionnaire. Using the VAS scale for nasal blockage, score the severity of complaints on each side independently. At each visit, evaluation of the healing process by rigid endoscopy and then by numerical scale. Results: On the 10th day lateralization was less in the HB group than in the B group (P value 0.033) and on the 30th day, crust formation was less in the HB group than in the B group (P value 0.031). There was a significant difference regarding synechiae on the 30th day that was less in HB group than B group (0.012). On the 30th day, the VAS scale for nasal obstruction was less in the HB group than in the B group (P value 0.022). Conclusions: In sino-nasal surgery, the use of absorbable nasal packing with hyaluronic acid and berberine hydrochloride improves patient comfort as well as the healing process. Nonetheless, more research is required to optimize it.