||Screening the aqueous extract of Symplocos racemosa bark demonstrated its broad spectrum antimicrobial potential with an average zone of inhibition 12–17mm. Using one-factor-at-a-time approach, 15% concentration, extraction for 20 min at 40 oC and a pH of 3.5 and filtration through Whatman filter paper, were found to be optimal for the best antimicrobial efficacy. Statistical optimization by response surface methodology enhanced the antimicrobial activity upto 1.3 folds. MIC values of the aqueous extract ranged from 5 –15 mg/ml. The viable cell count studies revealed P. aeruginosa to be the most sensitive and got killed instantaneously at 0 h. The aqueous extract was found to be reasonably thermostable at 100 °C for 1 h and had a better shelf life at refrigeration temperature (4 °C). Biosafety evaluation of the aqueous extract showed it to be neither cytotoxic nor mutagenic as revealed by Ames test and MTT assay, thus showing its promise for further pursuance.