In this study, in vitro antimicrobial activity of Polyherbal cream comprising of various plant herb extracts of leaves viz. Aloe barbadensis, Calendula officinalis, Lawsonia inermis, Carica Papaya and Azadirachta indica along with tridax procumbens as a key Plant was evaluated. Polyherbal formulations (F1 & F2) were designed and developed as ointment based semisolid cream. Disc diffusion method and agar well diffusion method were used for in vitro antibacterial and antifungal screening for both the formulations. Zone of inhibition were observed as a measure of investigation. The Formulation-1 (F1) showed efficient zone of inhibition at concentration of 4% than the formulation-2 (F2) at lower concentration 2% of tridax procumbens. In antifungal screening, the compound showed significant zones of inhibition against tested fungi.