A new series of 4-(3-arylureido)phenyl-1,4 dihydropyridine urea derivatives were synthesized using simple three component condensation, reduction, and nucleophilic addition sequence in moderate to good yields. All the synthesized compounds 6a–j were evaluated for their antiinflammatory [against the pro-inflammatory cytokines (tumor necrosis factor-alpha, TNF-a and interleukin-6, IL-6)] and anti-microbial activity (anti-bacterial and anti-fungal). Among all the compound screened, the compound 6b, 6f, and 6j were found to have promising anti-inflammatory activity, 74–83 % TNF-a and 91–96 % IL-6 inhibitory activity, respectively as compared to the standard dexamethasone (71 and 86 % inhibition) but at the MIC of 10 lM/ml. The compounds 6d–e and 6h exhibited relatively lower TNF-a and IL-6 inhibitory activity and found to be moderately potent anti-inflammatory agents. The compounds 6c–e, 6g, and 6i were found to be promising anti-bacterial and anti-fungal agents and remarkably some of the new compounds, viz. 6d and 6i were found be more potent than the standard ciprofloxacin or miconazole. It is to be noted that this is the first report on the anti-inflammatory activity evaluation of novel 1,4-dihydropyridine urea derivatives against the important molecular target, TNF-a, and IL-6.