Background and objectives: Chemotherapeutic agents have the potential to inhibit plaque growth, reduce gingivitis and improve oral health beyond tooth brushing alone. The aim of this study is to compare the therapeutic effectiveness of 0.2% hyaluronic acid-containing gel (Gengigel) with a 0.2% chlorhexidine containing gel effect, in the treatment of plaque induced gingivitis. Methods: This cross-sectional analytical case control study involved 150 generally healthy patients, age ranging 20-40 years, with gingivitis. The patients were divided in two groups, after scaling and polishing, 75 patients in each. The first group was given 0.2% hyaluronic acid containing gel and the second group was given 0.2 % chlorhexidine containing gel. Clinical examination, which included bleeding on probing, plaque index at the baseline, after 7 days and after 21 days were calculated. Antimicrobial properties of both gels in the saliva were measured by agar diffusion method. Results: No significant difference was detected between the two groups regarding the mean ranks of the Plaque index difference after a week (chlorhexidine group = 0.81, hyaluronic acid group = 0.89) and after three weeks (0.58, 0.54 respectively). The mean of the difference in Bleeding index after one week in the chlorhexidine group (39.44) were significantly higher than those (32.87) of the group of hyaluronic acid, But the difference was not significant after three weeks (37.40 and 37.27 respectively). The chlorhexidine group inhibition zone (19.2) was significantly higher than the hyaluronic acid group (10.6) Conclusions: in this study, the adjunctive use of 0.2 percent hyaluronic acid gel is comparable to 0.2 percent chlorhexidine gel for gingivitis treatment.