Abstract Various chemical agents have been evaluated over the years with respect to their antimicrobial effects in the oral cavity; however, all are associated with side effects that prohibit regular long-term use. Therefore, the effectiveness of neem ( Azadirachta indica A. Juss) leaf extract against plaque formation was assessed in males between the age group of 20–30 years over a period of 6 weeks. Present study includes formulation of mucoadhesive dental gel containing Azadirachta indica leaf extract (25 mg/g). A 6-week clinical study was conducted to evaluate the efficacy of neem extract dental gel with commercially available chlorhexidine gluconate (0.2% w/v) mouthwash as positive control. Microbial evaluation of Streptococcus mutans and Lactobacilli species was carried out to determine the total decrease in the salivary bacterial count over a period of treatment using a semi-quantitative four quadrant streaking method. The results of the study suggested that the dental gel containing neem extract has significantly ( P<0.05) reduced the plaque index and bacterial count than that of the control group.