The aim of this study was to prepare, characterize and evaluate liposomes co-encapsulated with curcumin and quercetin using a droplet-based microfluidic device. Curcumin and quercetin co-encapsulated liposomes made of phosphatidylcholine and cholesterol were synthesized using a droplet-based microfluidic device with different flow rate ratios of 9:1, 6:1, 3:1 and 1:1 of the aqueous to organic phase at 100 to 160 µl/min flow rate. The dynamic light scattering technique showed that 9:1 and 6:1 flow rate ratios at 140 and 160 µl/min flow rates, respectively provide desired particle size range of 200–250 nm and 0.17–0.23 polydispersity index. The greatest encapsulation and loading efficiency achieved for curcumin and quercetin was 68 ± 9.2%, 14 ± 1.8%, and 36 ± 2.7%, 7.2 ± 0.5%, respectively with 6:1 flow rate ratio. Cell uptake studies performed on human oral carcinoma cells, FaDu using confocal laser scanning microscopy showed that the liposomes were taken up within 2 h. Clathrin and caveolin-mediated pathways contribute to the cell uptake of liposomes. The FaDu cell viability was reduced to 49 ± 2.2, 69 ± 1.5 and 47 ± 3.5% after incubation with liposomes containing curcumin (80 µM), quercetin (86 µM) and combination (32 µM of curcumin and 26 µM of quercetin), respectively. Apoptosis assay showed that the combination liposomes inhibit FaDu cell growth through apoptosis induced cell death. In conclusion, co-encapsulated liposomes can be prepared by microfluidics-based method and curcumin and quercetin combination liposomes are effective against oral carcinoma.