Background: There is an urgent need for innovative strategies to combat the two most common dental diseases of mankind namely dental caries and periodontitis. Objective: The aim was to assess the antimicrobial efficacy of the double combinations of Acacia nilotica (AN), Murraya koenigii L. Sprengel (MKL), Eucalyptus hybrid and Psidium guajava on primary plaque colonizers. Materials and Methods: The plant extracts of AN, MKL. Sprengel, Eucalyptus hybrid and P. guajava were prepared using Soxhlet apparatus. The stock solutions of individual plant extracts (100 mg/ml) were prepared. Equal quantities of stock solutions were mixed to obtain six double combinations of herbal extracts. The antimicrobial efficacy testing was done against three primary plaque colonizers using agar wellâdiffusion method. 0.2% chlorhexidine and dimethyl sulfoxide were used as positive and as negative controls. The mean inhibition zone between the categories was compared using oneâway Analysis of Variance and Tukey’s post hoc test. Results: The combination of AN and P. guajava produced the highest mean diameter of inhibition zone (21.08 mm ± 2.11) against Streptococcus mutans. The chlorhexidine produced the least inhibition zone against S. mutans (14.50 ± 2.07). The combination of AN and P. guajava produced the maximum antimicrobial efficacy against Streptococcus sanguis (19.67 ± 1.03) and Streptococcus salivarius (20.33 ± 1.86). Conclusion: All the combinations of plant extracts have the potential to be used as antiplaque and anticaries agents. The combinations of herbal extracts offer enhanced antimicrobial efficacy due to the synergistic effects besides slowing the development of resistance.