According to Ayurveda, individual herbs are insufficient to achieve a desired therapeutic effect. When it is optimized as multiple herbs composition in a particular ratio it will give a therapeutic effect in a better way with reduced toxicity. In order to develop such an intervention, the present study was intended to develop a polyherbal drug from methanolic extracts of Plumbago zeylanica Linn, Datura stramonium Linn and Argemone mexicana Linn. The study also aimed to evaluate the impact of polyherbalism on antimicrobial and antioxidant effect, thereafter the ratio of individual plant extracts was optimized accordingly to treat the wound. The poyherbal drug was put on preclinical trial to access the anti-inflammatory and wound healing activity as 2% and 5% polyherbal carbopol-940 gels. The antimicrobial activity was assessed by agar well diffusion and broth dilution method while wound healing activity was evaluated by excision and incision wound models. Topical anti-inflammatory activity was assessed by carrageenan induced paw oedema. The findings of the study revealed the synergistic antimicrobial potential of Polyherbal drug against gram-positive and negative strains. Polyherbal carbopol- 940 gels (2% and 5%w/w) promoted the wound healing and anti-inflammatory effect. The high rate of wound contraction (<0.0001), early epithelialization period (<0.0001) and increased wound breaking strength (<0.0001) were observed in 2% and 5% polyherbal gel treated group when compared to the normal control and negative control group. The antimicrobial and anti-inflammatory effect of Polyherbal drug provoked and promoted the wound healing process through accelerated remodelling of damaged tissue.