OBJECTIVE The study aimed to assess the impact of mouthwashes on antibacterial activity of individuals with fixed orthodontic appliances. METHODS A total of 60 individuals were considered in the study. Sixty (20 each group) nonextraction class I individuals were randomly divided into experimental and control groups. Group I: Experimental group [chlorhexidine (CHX) mouthwash], group II: Experimental group (neem mouthwash), group III: Control group (distilled water). All the clinical examinations were done at baseline and 30th day respectively, after the start of orthodontic treatment. The mean differences between the different experimental groups were calculated using one-way analysis of variance (ANOVA) test. RESULTS There was no statistical significance at baseline mean plaque index (PI), gingival index (GI) scores, and Streptococcus mutans (SM) colony count between groups. The PI and GI scores among CHX and neem mouthwash groups (p = 0.002, p = 0.032 respectively) were significantly reduced after intervention and also the SM colonies count was reduced in CHX and neem mouthwash groups and there was significant difference between the groups. CONCLUSIONS As both mouthwashes showed significant effectiveness on antibacterial activity in individuals with fixed orthodontic appliances, neem mouthwash can be used as an alternative to CHX. CONCLUSIONS It is better to have a sound knowledge regarding the use of mouthwash in long term as fixed orthodontics are associated with accumulation of SM, enamel demineralization, and an increased number of carious lesions, predominantly in sites adjacent to bracket.