Oral candidiasis is an opportunistic infection seen in debilitated and immunocompromised patients. In the current study, an innovative drug delivery system comprising of mucoadhesive buccal films to reduce the drug dosing frequencyand improvebioavailability was employed. An unconventional preparation of quercetin and theantimycoticdrug, clotrimazole was prepared and impregnated in buccal mucosal films prepared by the casting method. The physical properties of the filmswere studied. Minimum inhibitory concentration of quercetin and clotrimazole was determined by the broth macrodilution method and was found to be 50 mg/ml and 15 μg/ml respectively. The combined action of the two drugs was assessed by the checkerboard assay. The fractional inhibitory concentration index obtained was 0.5, which indicated synergistic action between the two compounds. Fourier transformed infrared spectroscopy (FTIR) studies revealed no change in the properties of flavonoid quercetin and drug clotrimazole post impregnation in mucoadhesive patches. Ex vivo experiments were performed using goat skin and significant reduction of 97.7 percent was observed in the viability of Candida albicans using a combination of the two antimicrobial compounds. This current study helps to establish a novel treatment regimen for oral candidiasis using an innovative drug delivery system which can provide better patient compliance and therapeutic efficacy.