Purpose: The present study compared the antiplaque effects of two herbal mouthwashes containing Salvadora persica and Azadirachta indica, respectively, with two synthetic mouthwashes containing either chlorhexidine or cetylpyridinium. Materials and Methods: In this triple-blind, randomised controlled trial, 100 patients undergoing orthodontic treatment underwent scaling and polishing at baseline to obtain a plaque score of zero. In the first phase, they were given oral hygiene instructions and were provided with a standard toothpaste to be used twice daily for a period of three weeks. In the second phase, following scaling and polishing, they were randomly allocated to 4 groups according to 4 different types of mouthwash (A: chlorhexidine; B = cetylpyridinium; C = extracts of Salvadora persica miswak; D: extract of Azadirachta indica miswak) along with previously taught toothbrushing protocol for three more weeks. Plaque accumulation was scored three times according to the Modified Bonded Bracket Plaque Index: at the start, after the toothbrush-toothpaste trial, and at the end of mouthwash trial. The paired t-test was used to compare the pre-plaque and post-plaque indices in all groups. Analysis of mean differences of post-plaque indices between and within groups was performed using the post-hoc Tukey test. Qualitative variables were compared by Crosstab. Results: Eighty participants completed the study - 63 females and 17 males. There was a statistically significant decrease in mean plaque scores after using mouthwashes in all four groups at follow-up when compared to the baseline plaque score (p = 0.001). The greatest reduction of plaque score was found in group C (extract of Salvadora persica) when compared with group A, chlorhexidine (p = 0.016). Conclusion: Compared to other mouthwashes, Salvadora persica miswak-based mouthwash showed a maximum reduction in the plaque scores among orthodontic patients. Keywords: Azadirachta indica (neem), cetylpyridinium (CPC), chlorhexidine (CHX), dental plaque, herbal mouthwash, Salvadora persica (peelu)